Neurogenetics via MedWorm.com MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Neurogenetics' source. Mon, 06 Feb 2012 09:32:19 +0100 Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees and a case-control cohort http://www.medworm.com/index.php?rid=5663334&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj6t4421011094k34%2F Abstract  Investigations into migraine genetics have suggested that susceptibility loci exist on the X chromosome. These reports are supported by evidence that demonstrates male probands as having a higher proportion of affected first-degree relatives as well as the female preponderance of 3:1 that the disorder displays. We have previously implicated the Xq24-28 locus in migraine using two independent multigenerational Australian pedigrees that demonstrated excess allele sharing at the Xq24, Xq27 and Xq28 loci. Here, we expand this work to investigate a further six independent migraine pedigrees using 11 microsatellite markers spanning the Xq27–28 region. Furthermore, 11 candidate genes are investigated in an Australian case-control cohort consisting of 500 cases and 500 ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5663334 Tue, 31 Jan 2012 16:46:53 +0100 5663334 Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) http://www.medworm.com/index.php?rid=5654687&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr6316137w8031056%2F Abstract  We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis, intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability. Content Type Journal ArticleCategory Original ArticlePages 1-4DOI 10.1007/s10048... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5654687 Mon, 30 Jan 2012 16:07:44 +0100 5654687 Neuroferritinopathy: a new inborn error of iron metabolism http://www.medworm.com/index.php?rid=5654688&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj41mt574h5288706%2F Abstract  Neuroferritinopathy is an autosomal dominant progressive movement disorder which occurs due to mutations in the ferritin light chain gene (FTL1). It presents in mid-adult life and is the only autosomal dominant disease in a group of conditions termed neurodegeneration with brain iron accumulation (NBIA). We performed brain MRI scans on 12 asymptomatic descendants of known mutation carriers. All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA. Content Type Journal ArticleCategory Short CommunicationPages 1-4DOI 10.1007/s10048-011-0310-9Authors Michael J. Keogh, Institute of Genet... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5654688 Wed, 25 Jan 2012 18:14:59 +0100 5654688 Vincristine exacerbates asymptomatic Charcot–Marie–Tooth disease with a novel EGR2 mutation http://www.medworm.com/index.php?rid=5642409&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3g578vlq65842112%2F Abstract  Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported in patients with Charcot–Marie–Tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed resequencing array that simultaneous... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5642409 Tue, 24 Jan 2012 07:36:18 +0100 5642409 Distinct DNA binding and transcriptional repression characteristics related to different ARX mutations http://www.medworm.com/index.php?rid=5615644&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F62227660425720v2%2F Abstract  Mutations in the Aristaless-related homeobox gene (ARX) are associated with a wide variety of neurologic disorders including lissencephaly, hydrocephaly, West syndrome, Partington syndrome, and X-linked intellectual disability with or without epilepsy. A genotype–phenotype correlation exists for ARX mutations; however, the molecular basis for this association has not been investigated. To begin understanding the molecular basis for ARX mutations, we tested the DNA binding sequence preference and transcriptional repression activity for Arx, deletion mutants and mutants associated with various neurologic disorders. We found DNA binding preferences of Arx are influenced by the amino acid sequences adjacent to the homeodomain. Mutations in the homeodomain show a loss ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5615644 Wed, 18 Jan 2012 06:59:18 +0100 5615644 Genome-scale methylation analysis of Parkinson's disease patients' brains reveals DNA hypomethylation and increased mRNA expression of cytochrome P450 2E1 http://www.medworm.com/index.php?rid=5590875&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx14x6x1x4638g522%2F We present a genome-wide methylation analysis of PD with quantitative DNA methylation levels of 27.500 CpG sites representing 14.495 genes. We found decreased methylation of the cytochrome P450 2E1 gene and increased expression of CYP2E1 messenger RNA in PD patients' brains, suggesting that epigenetic variants of this cytochrome contribute to PD susceptibility. Content Type Journal ArticleCategory Short CommunicationPages 1-5DOI 10.1007/s10048-011-0308-3Authors Oliver Kaut, University Clinic, Department of Neurology, University of Bonn, Bonn, GermanyIna Schmitt, University Clinic, Department of Neurology, DZNE, German Center for Neurodegenerative Diseases, University of Bonn, Bonn, GermanyUllrich Wüllner, University Clinic, Department of Neurology, University of Bonn, Bonn, Germ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5590875 Wed, 11 Jan 2012 17:53:21 +0100 5590875 Pathomechanistic characterization of two exonic L1CAM variants located in trans in an obligate carrier of X-linked hydrocephalus http://www.medworm.com/index.php?rid=5575508&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F04g6265082724632%2F We report here a family case of X-linked hydrocephalus in which an obligate female carrier has two exonic L1CAM missense mutations in trans substituting amino acids in the first (p.W635C) or second (p.V768I) fibronectin-type III domains. We performed various biochemical and cell biological in vitro assays to evaluate the pathogenicity of these variants. Mutant L1-W635C protein accumulates in the endoplasmic reticulum (ER), is not transported into axons, and fails to promote L1CAM-mediated cell–cell adhesion as well as neurite growth. Immunoprecipitation experiments show that L1-W635C associates with the molecular ER chaperone calnexin and is modified by poly-ubiquitination. The mutant L1-V768I protein localizes at the cell surface, is not retained in the ER, and promotes neurite gr... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5575508 Thu, 05 Jan 2012 17:05:39 +0100 5575508 Genotype–phenotype correlation in interstitial 6q deletions: a report of 12 new cases http://www.medworm.com/index.php?rid=5567088&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff65624264lqxhj26%2F We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick cor... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5567088 Wed, 04 Jan 2012 17:00:00 +0100 5567088 New brain-specific beta-synuclein isoforms show expression ratio changes in Lewy body diseases http://www.medworm.com/index.php?rid=5556113&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk86t7x4657287725%2F In this study, we characterized four new BS transcript variants and analyzed their expression in neuronal and non-neuronal tissue, and their differential expression in frozen samples of three areas from brains of patients with pure Lewy body pathology (LBP), common LBP, Alzheimer pathology, and of controls. Relative mRNA expression was determined by real-time PCR with neuron-specific enolase 2 and synaptophysin as housekeeping genes, and expression changes were evaluated by the ΔΔCt method. Two main findings are in concordance with earlier studies. First, all BS isoforms are drastically diminished in the cortex of patients with pure LBP that had presented clinically as DLB but not PD with dementia. Second, an important shift of the isoform expression ratio was observed in the tempo... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5556113 Wed, 28 Dec 2011 16:53:31 +0100 5556113 Comment on the article “Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri” by van den Munckhof et al. http://www.medworm.com/index.php?rid=5556114&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb3713477501858u2%2F Content Type Journal ArticleCategory Letter to the EditorsPages 1-2DOI 10.1007/s10048-011-0309-2Authors Trine E. Prescott, Department of Medical Genetics, Oslo University Hospital, Oslo, NorwayMiriam J. Smith, Department of Genetic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Oxford Road, Manchester, M13 9WL UKD. Gareth Evans, Department of Genetic Medicine, St Mary’s Hospital, Manchester Academic Health Sciences Centre (MAHSC), University of Manchester, Oxford Road, Manchester, M13 9WL UK Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5556114 Tue, 27 Dec 2011 17:04:00 +0100 5556114 Independent replication of STAT3 association with multiple sclerosis risk in a large German case–control sample http://www.medworm.com/index.php?rid=5436139&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr9514vw301856238%2F This study supports the association between STAT3 and an increase in MS risk. Taking into account the functional role of STAT3, our results favour an involvement of Th17 lymphocytes in MS. Content Type Journal ArticleCategory Short CommunicationPages 1-4DOI 10.1007/s10048-011-0305-6Authors Christina M. Lill, Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, GermanyBrit-Maren M. Schjeide, Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, GermanyDenis A. Akkad, Department of Human Genetics, Ruhr University, Bochum, GermanyPaul Blaschke, Department of Neurology, University of Rostock, Rostock, GermanyAlexander Winkelmann, Department of Neurology, University of Rostock, Rost... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5436139 Fri, 18 Nov 2011 06:57:52 +0100 5436139 Acknowledgement to Referees 2010/2011 http://www.medworm.com/index.php?rid=5372173&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9003328u85745533%2F Content Type Journal ArticleCategory ACKNOWLEDGEMENT TO REFEREESPages 1-2DOI 10.1007/s10048-011-0301-x Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5372173 Mon, 31 Oct 2011 16:59:21 +0100 5372173 Germline SMARCB1 mutation predisposes to multiple meningiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri http://www.medworm.com/index.php?rid=5372174&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpm642777u62w1474%2F Abstract  Schwannomatosis is a rare hereditary cancer syndrome in which patients develop multiple non-vestibular schwannomas. The chromatin remodelling gene SMARCB1 (also known as INI1, hSNF5, and BAF47) has been identified as a schwannomatosis predisposing gene, being involved in a subset of sporadic and familial cases. Recent studies have shown that SMARCB1 may also be involved in the development of multiple meningiomas. Previously, we demonstrated that the SMARCB1 exon 2 missense mutation c.143 C > T segregates with the presence of meningiomas in five members of a large family with multiple meningiomas and schwannomas. We extended our genetic analyses by screening 44 additional at-risk family members and identified 13 new carriers. Eleven of these were subjecte... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5372174 Fri, 28 Oct 2011 17:24:31 +0100 5372174 Restriction of trophic factors and nutrients induces PARKIN expression http://www.medworm.com/index.php?rid=5372175&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd2h5j722x2767111%2F In conclusion, this expression survey demonstrates that PARKIN and PINK1 are coregulated during starvation and suggest a role of both PD genes in response to trophic signals and starvation stress. Content Type Journal ArticleCategory ORIGINAL ARTICLEPages 1-13DOI 10.1007/s10048-011-0303-8Authors M. Klinkenberg, Experimental Neurology, Department of Neurology, University Medical School, Goethe University, Heinrich-Hoffmann-Str. 7, 60528 Frankfurt am Main, GermanyS. Gispert, Experimental Neurology, Department of Neurology, University Medical School, Goethe University, Heinrich-Hoffmann-Str. 7, 60528 Frankfurt am Main, GermanyJ. A. Dominguez-Bautista, Experimental Neurology, Department of Neurology, University Medical School, Goethe University, Heinrich-Hoffmann-Str. 7, 60528 Frankfu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5372175 Wed, 26 Oct 2011 05:46:28 +0100 5372175 Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations http://www.medworm.com/index.php?rid=5320117&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv6064k5045uj57t3%2F Abstract  Early-onset Parkinson’s disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low c... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5320117 Wed, 12 Oct 2011 16:06:59 +0100 5320117 New mutations in the ATM gene and clinical data of 25 AT patients http://www.medworm.com/index.php?rid=5280057&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F13635771847n0n44%2F Abstract  Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar degeneration, immunodeficiency, oculocutaneous telangiectasias, chromosomal instability, radiosensitivity, and cancer predisposition. The gene mutated in the patients, ATM, encodes a member of the phosphatidylinositol 3-kinase family proteins. The ATM protein has a key role in the cellular response to DNA damage. Truncating and splice site mutations in ATM have been found in most patients with the classical AT phenotype. Here we report of our extensive ATM mutation screening on 25 AT patients from 19 families of different ethnic origin. Previously unknown mutations were identified in six patients including a new homozygous missense mutation, c.8110T>C (p.Cys2704Arg), in a se... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5280057 Sat, 01 Oct 2011 05:43:39 +0100 5280057 Shorter telomeres in patients with cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL) http://www.medworm.com/index.php?rid=5189770&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw508454u26229m57%2F Abstract  CADASIL is a hereditary systemic vasculopathy which affects mainly small cerebral arteries and is caused by mutations in the Notch3 gene. Misfolding of Notch3 is linked to endoplasmic reticulum stress and increased reactive oxygen species, which may result in dysfunction of endothelial cells, inflammation and ischemia. Oxidative stress and inflammation may induce a rapid telomere shortening in peripheral blood leukocytes (PBLs). The aim of this study was to assess the telomere length in PBLs from 29 patients with a genetic diagnosis of CADASIL by using a modified quantitative real-time polymerase chain reaction based assay. PBL telomere length was significantly shorter in CADASIL patients (T/S ratio = 0.17, 95% CI, 0.14–0.20) than in the controls (T/S ratio... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5189770 Wed, 31 Aug 2011 15:54:43 +0100 5189770 Social responsiveness scale-aided analysis of the clinical impact of copy number variations in autism http://www.medworm.com/index.php?rid=5129382&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1771rw610r31157x%2F Abstract  Recent array-based studies have detected a wealth of copy number variations (CNVs) in patients with autism spectrum disorders (ASD). Since CNVs also occur in healthy individuals, their contributions to the patient’s phenotype remain largely unclear. In a cohort of children with symptoms of ASD, diagnosis of the index patient using ADOS-G and ADI-R was performed, and the Social Responsiveness Scale (SRS) was administered to the index patients, both parents, and all available siblings. CNVs were identified using SNP arrays and confirmed by FISH or array CGH. To evaluate the clinical significance of CNVs, we analyzed three families with multiple affected children (multiplex) and six families with a single affected child (simplex) in which at least one child carried... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5129382 Fri, 12 Aug 2011 06:10:57 +0100 5129382 Homozygosity for the MTX1 c.184T>A (p.S63T) alteration modifies the age of onset in GBA-associated Parkinson's disease http://www.medworm.com/index.php?rid=5129381&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F94x755804287h213%2F Abstract  A strong association was established between the GBA gene and Parkinson's disease (PD) worldwide. The most frequent GBA mutation among the Ashkenazi population (p.N370S) was previously associated with the c.1051T>C (p.F351L) alteration in the closely located MTX1 gene. We further studied the association between these two genes and its possible effect on PD. The entire coding region and exon–intron boundaries of MTX1 were analyzed in 81 PD patient carriers of GBA mutations, 15 healthy controls that carry GBA mutations, and in 25 non-carrier patients. Among them, the MTX1 c.184T>A (p.S63T) variation was detected in 93% of GBA mutation carriers (both patients and healthy controls) and in 64% of non-carrier patients (p = 0.0008). This alteration was analyzed i... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5129381 Fri, 12 Aug 2011 06:10:57 +0100 5129381 A novel deletion–insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype http://www.medworm.com/index.php?rid=5123654&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fawk3318335337882%2F Abstract  Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease most commonly caused by a GAA trinucleotide repeat expansion in the first intron of FXN, which reduces expression of the mitochondrial protein frataxin. Approximately 98% of individuals with FRDA are homozygous for GAA expansions, with the remaining 2% compound heterozygotes for a GAA expansion and a point mutation within FXN. Two siblings with early onset of symptoms experienced rapid loss of ambulation by 8 and 10 years. Diagnostic testing for FRDA demonstrated one GAA repeat expansion of 1010 repeats and one non-expanded allele. Sequencing all five exons of FXN identified a novel deletion-insertion mutation in exon 3 (c.371_376del6ins15), which results in a modified frataxin protein ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5123654 Wed, 10 Aug 2011 15:45:37 +0100 5123654 Late-onset Alzheimer's disease is associated with mitochondrial DNA 7028C/haplogroup H and D310 poly-C tract heteroplasmy http://www.medworm.com/index.php?rid=5115592&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe0477150l4155343%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s10048-011-0295-4Authors Eliecer Coto, Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, 33006 Oviedo, SpainJuan Gómez, Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, 33006 Oviedo, SpainBelén Alonso, Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, 33006 Oviedo, SpainAna I. Corao, Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, 33006 Oviedo, SpainMarta Díaz, Genética Molecular-Laboratorio de Medicina, Hospital Universitario Central Asturias, 33006 Oviedo, SpainManuel Menéndez, Neurología, Hospital A Buylla, Mieres, SpainCarmen Martínez, Neurología, Hospital Cabueñes, Gijón, SpainM... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5115592 Sun, 07 Aug 2011 05:51:35 +0100 5115592 Genetic variability in SNCA and Parkinson’s disease http://www.medworm.com/index.php?rid=5084501&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr6812q57333v6238%2F Abstract  Over the last decades, increasing knowledge about the genetic architecture of Parkinson’s disease has provided novel insights into the pathogenesis of the disorder, generating hypotheses for further research. Characterizing the role of SNCA, encoding the α-synuclein protein, has been a particularly important aspect of this development. The identification of SNCA as the first gene implicated in monogenic parkinsonism led to the recognition of α-synuclein as a key protein in the pathogenesis and a major component of pathological hallmark lesions. An association between common variants in SNCA and risk of sporadic Parkinson’s disease has been established through numerous studies. We review our current understanding of SNCA variability contributing to Parkinson’s... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5084501 Thu, 28 Jul 2011 15:56:24 +0100 5084501 Up-regulation of metallothionein gene expression in Parkinsonian astrocytes http://www.medworm.com/index.php?rid=5084502&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F86022m73075546g1%2F Abstract  The role of glial cells in Parkinson’s disease (PD) is unclear. We have previously reported a striking up-regulation of DnaJB6 heat shock protein in PD substantia nigra astrocytes. Whole genome transcriptome analysis also indicated increased expression of metallothionein genes in substantia nigra and cortex of sporadic PD cases. Metallothioneins are metal-binding proteins in the CNS that are released by astrocytes and associated with neuroprotection. Metallothionein expression was investigated in 18 PD cases and 15 non-PD controls using quantitative real-time polymerase chain reaction (qRT-PCR), in situ hybridisation (ISH) and immunocytochemistry (ICC). We observed a strong increase in the expression of metallothioneins MT1E, MT1F, MT1G, MT1H, MT1M, MT1X and MT2... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5084502 Thu, 28 Jul 2011 15:56:20 +0100 5084502 A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18) http://www.medworm.com/index.php?rid=5075056&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu1u74r15u881801g%2F We describe an extended consanguineous Saudi family in which HSP is linked to SPG18, a previously reported autosomal recessive locus, and show that it is associated with a nullimorphic deletion of ERLIN2, a component of endoplasmic reticulum associated degradation. This finding adds to the growing diversity of cellular functions that are now known to be involved in the maintenance of the corticospinal tract neurons. Content Type Journal ArticlePages 1-4DOI 10.1007/s10048-011-0291-8Authors Anas M. Alazami, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaNouran Adly, Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi ArabiaHisham Al Dhalaan, Department of Neurosciences, King Faisal Specialist H... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5075056 Wed, 27 Jul 2011 15:47:26 +0100 5075056 Differentially expressed genes in hypothalamus in relation to genomic regions under selection in two chicken lines resulting from divergent selection for high or low body weight http://www.medworm.com/index.php?rid=5034561&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh522242414277513%2F Abstract  Long-term divergent selection for low or high body weight from the same founder population has generated two extremely divergent lines of chickens, the high- (HWS) and low-weight (LWS) selected lines. At selection age (56 days), the lines differ by more than nine times in body weight. The HWS line chickens are compulsive feeders, whereas in the LWS line, some individuals are anorexic and others have very low appetite. Previous studies have implicated the central nervous system and particularly the hypothalamus in these behavioural differences. Here, we compared the mRNA expression in hypothalamus tissue from chickens on day 4 post-hatch using oligonucleotide arrays and found that the divergent selection had resulted in minor but multiple expression diffe... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=5034561 Tue, 12 Jul 2011 06:00:46 +0100 5034561 Audiogenic seizure proneness requires the contribution of two susceptibility loci in mice http://www.medworm.com/index.php?rid=4950544&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc706h53p1242u004%2F Abstract  Juvenile mice of the DBA/2J strain undergo generalised seizures when exposed to a high-intensity auditory stimulus. Genetic analysis identified three different loci underlying this audiogenic seizure proneness (ASP)—Asp1, Asp2 and Asp3 on chromosomes 12, 4 and 7, respectively. Asp1 is thought to have the strongest influence, and mice with only Asp1 derived from the DBA/2J strain are reported to exhibit ASP. The aim of this study was to characterise more accurately the contributions of the Asp1 and Asp3 loci in ASP using congenic strains. Each congenic strain contains a DBA/2J-derived interval encompassing either Asp1 or Asp3 on a C57BL/6J genetic background. A double congenic C57BL/6J strain containing both Asp loci derived from DBA/2J was also generated. Here, we r... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4950544 Fri, 17 Jun 2011 12:02:11 +0100 4950544 Broadening the phenotype of TARDBP mutations: the TARDBP Ala382Thr mutation and Parkinson’s disease in Sardinia http://www.medworm.com/index.php?rid=4930476&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0j3732851j67447w%2F In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD. Content Type Journal ArticlePages 1-7DOI 10.1007/s10048-011-0288-3Authors Marialuisa Quadri, Department of Clinical Genetics, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The NetherlandsGiovanni Cossu, Neurology Service and Stroke Unit, General Hospital S. Michele AOB “G. Brotzu”, Piazzale Ricchi 1, 09134 Cagliari, ItalyValeria Saddi, Neurology Division, S. Francesco Hospital, ASL No. 3 Nuoro, ItalyErik J. Simons, Department of Clinical Genetics, Erasmus MC, P.O. Box 2040... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4930476 Sat, 11 Jun 2011 06:35:47 +0100 4930476 A novel mitofusin 2 mutation causes canine fetal-onset neuroaxonal dystrophy http://www.medworm.com/index.php?rid=4918929&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmw1718888579k43m%2F Abstract  We recently reported autosomal recessive fetal-onset neuroaxonal dystrophy (FNAD) in a large family of dogs that is not caused by mutation in the PLA2G6 locus (Fyfe et al., J Comp Neurol 518:3771–3784, 2010). Here, we report a genome-wide linkage analysis using 333 microsatellite markers to map canine FNAD to the telomeric end of chromosome 2. The interval of zero recombination was refined by single-nucleotide polymorphism (SNP) haplotype analysis to ~200 kb, and the included genes were sequenced. We found a homozygous 3-nucleotide deletion in exon 14 of mitofusin 2 (MFN2), predicting loss of a glutamate residue at position 539 in the protein of affected dogs. RT-PCR demonstrated near normal expression of the mutant mRNA, but MFN2 expression was undetectable ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4918929 Sat, 04 Jun 2011 05:52:22 +0100 4918929 Autozygosity mapping of a large consanguineous Pakistani family reveals a novel non-syndromic autosomal recessive mental retardation locus on 11p15-tel http://www.medworm.com/index.php?rid=4918930&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5p18720100627164%2F Abstract  Autosomal recessive inherited mental retardation is an extremely heterogeneous disease and accounts for approximately 25% of all non-syndromic mental retardation cases. Autozygosity mapping of a large consanguineous Pakistani family revealed a novel locus for non-syndromic autosomal recessive mental retardation (NS-ARMR). The affected individuals showed low IQ and cognitive impairment without any neurological, skeletal, and biochemical abnormalities. All known NS-ARMR genes were excluded by STS markers, so autozygosity mapping by microarray single-nucleotide polymorphism (SNP) analysis were done in all sampled individuals in the family. The nuclear central loop in the five generation family showed homozygosity for a 6-Mb telomeric region on 11p15, whereas all othe... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4918930 Sat, 04 Jun 2011 05:52:20 +0100 4918930 Call for participation in the neurogenetics consortium within the Human Variome Project http://www.medworm.com/index.php?rid=4900156&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F660mkg1115r86328%2F This report outlines the strategic aims established at the preliminary meetings of the Neurogenetics Consortium and calls for the involvement of the wider neurogenetic community in enabling the development of this important resource. Content Type Journal ArticlePages 1-5DOI 10.1007/s10048-011-0287-4Authors Andrea Haworth, Neurogenetics Unit, Department of Molecular Neurosciences, National Hospital of Neurology and Neurosurgery, Queen Square, London, UKLars Bertram, Neuropsychiatric Genetic Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, Berlin, GermanyPaola Carrera, San Raffaele Scientific Institute, Center for Translational Genomics and Bioinformatics, Unit of Genomics for Human Disease Diagnosis and Laboraf, Milan, ItalyJoanna L. Elson, Mitochondrial Research G... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4900156 Wed, 01 Jun 2011 05:59:43 +0100 4900156 FGF17, a gene involved in cerebellar development, is downregulated in a patient with Dandy–Walker malformation carrying a de novo 8p deletion http://www.medworm.com/index.php?rid=4730820&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4040878215543737%2F Abstract  Fibroblast growth factors (FGFs) are important signaling molecules which act during early vertebrate central nervous system development. FGF17, together with FGF8, is a key factor in the patterning of the mid-hindbrain region with a complex picture of spatiotemporal gene expression during the various stages of cerebellar development. Disruption or reduced expression of fgf17 in mice has been associated with cerebellar vermis abnormalities. We have identified a de novo 2.3-Mb deletion of chromosome 8p21.2-p21.3 in a girl with severe growth retardation, seizures, and classical Dandy–Walker malformation. Analysis of gene expression in blood lymphocytes and skin fibroblasts revealed markedly reduced levels of FGF17, which is located 1 Mb from the proximal deletion... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4730820 Tue, 12 Apr 2011 05:59:35 +0100 4730820 Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5 http://www.medworm.com/index.php?rid=4730821&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb1072p3308426m81%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s10048-011-0284-7Authors Takashi Matsukawa, Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 JapanXuemin Wang, School of Biological Sciences, Life Sciences Building, University of Southampton, Southampton, UKRui Liu, School of Biological Sciences, Life Sciences Building, University of Southampton, Southampton, UKNoel C. Wortham, School of Biological Sciences, Life Sciences Building, University of Southampton, Southampton, UKYuko Onuki, Department of Neurology, Graduate School of Medicine, University of Tokai, Kanagawa, JapanAkatsuki Kubota, Department of Neurology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655 JapanAyum... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4730821 Tue, 12 Apr 2011 05:59:34 +0100 4730821 Ataxia with oculomotor apraxia type1 (AOA1): novel and recurrent aprataxin mutations, coenzyme Q10 analyses, and clinical findings in Italian patients http://www.medworm.com/index.php?rid=4691534&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb66118364259tx18%2F Abstract  Ataxia with oculomotor apraxia type1 (AOA1, MIM 208920) is a rare autosomal recessive disease caused by mutations in the APTX gene. We screened a cohort of 204 patients with cerebellar ataxia and 52 patients with early-onset isolated chorea. APTX gene mutations were found in 13 ataxic patients (6%). Eleven patients were homozygous for the known p.W279X, p.W279R, and p.P206L mutations. Three novel APTX mutations were identified: c.477delC (p.I159fsX171), c.C541T (p.Q181X), and c.C916T (p.R306X). Expression of mutated proteins in lymphocytes from these patients was greatly decreased. No mutations were identified in subjects with isolated chorea. Two heterozygous APTX sequence variants (p.L248M and p.D185E) were found in six families with ataxic phenotype. Analyses of c... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4691534 Tue, 05 Apr 2011 10:00:13 +0100 4691534 Genotype–phenotype correlations in sepiapterin reductase deficiency. A splicing defect accounts for a new phenotypic variant http://www.medworm.com/index.php?rid=4640339&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1t02007g827h241%2F Abstract  Sepiapterin reductase (SR) catalyzes the final step in the de novo synthesis of tetrahydrobiopterin, essential cofactor for phenylalanine, tyrosine, and tryptophan hydroxylases. SR deficiency is a very rare disease resulting in monoamine neurotransmitter depletion. Most patients present with clinical symptoms before the first year of age corresponding to a dopa-responsive dystonia phenotype with diurnal fluctuations, although some patients exhibit more complex motor and neurological phenotypes. Herein, we describe four new cases from Spain, their clinical phenotype and the biochemical and genetic analyses. Two mutations in the SPR gene were functionally expressed to provide a basis to establish genotype–phenotype correlations. Mutation c.751A>T is functionally... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4640339 Thu, 24 Mar 2011 07:32:52 +0100 4640339 Pathological mechanisms and parent-of-origin effects in hereditary paraganglioma/pheochromocytoma (PGL/PCC) http://www.medworm.com/index.php?rid=4577601&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F906m6l1kh3982163%2F This article gives an overview of PGL/PCC in the context of the anatomy and function of paraganglia. It describes SDH, the genes encoding SDH, and provides information on genetic mechanisms in hereditary PGL/PCC. A model is proposed to explain exclusive paternal inheritance and loss of the maternal (putatively imprinted) allele as a prerequisite for tumor formation in PGLs 1 and 2. Content Type Journal ArticlePages 1-7DOI 10.1007/s10048-011-0280-yAuthors Ulrich Müller, Institut für Humangenetik, Justus-Liebig-Universität, Gießen, and bio.logis, Zentrum für Humangenetik, Frankfurt a.M., 35392 Giessen, Germany Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4577601 Wed, 09 Mar 2011 16:51:01 +0100 4577601 A new missense GDAP1 mutation disturbing targeting to the mitochondrial membrane causes a severe form of AR-CMT2C disease http://www.medworm.com/index.php?rid=4548650&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F064xm4h0330377u2%2F In this study, we characterize the CMT phenotype in one Polish family with recessive trait of inheritance at the clinical, electrophysiological, morphological, cellular, and genetic level associated with a new Gly327Asp mutation in the GDAP1 gene. In spite of the nature of Gly327Asp mutation (missense), the CMT phenotype associated with this variant may be characterized as an early onset, severe axonal neuropathy, with severe skeletal deformities. The mutation lies within the transmembrane domain of GDAP1 and interferes with the mitochondrial targeting of the protein, similar to the loss of the domain in the previously reported Q163X and S194X mutations. We conclude that the loss of mitochondrial targeting is associated with a severe course of disease. Our study shows that clinical o... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4548650 Wed, 02 Mar 2011 07:46:31 +0100 4548650 Familial spinal neurofibromatosis due to a multiexonic NF1 gene deletion http://www.medworm.com/index.php?rid=4548649&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg587710q40463257%2F We report the detailed clinical presentation and molecular features of a spinal neurofibromatosis familial case where a 40-year-old woman, presenting with multiple bilateral spinal neurofibromas and no other clinical feature of neurofibromatosis type 1 (NF1), inherited a paternal large multiexonic deletion (c.5944−?_7126+?del) which resulted in NF1 gene haploinsufficiency at the RNA level. In the clinically unaffected 73-year-old father, spinal cord MRI disclosed bilateral and symmetrical hypertrophy of spinal lumbosacral roots. Our study widens the phenotypic and mutational spectrum of NF1 and illustrates the difficulties of counseling patients with border-line or atypical presentation of this disorder. Content Type Journal ArticlePages 1-8DOI 10.1007/s10048-011-0278-5Authors ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4548649 Wed, 02 Mar 2011 07:46:31 +0100 4548649 Identification of a novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features http://www.medworm.com/index.php?rid=4488044&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp563ww7523712780%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s10048-011-0277-6Authors Nils Rademacher, Max Planck Institute for Molecular Genetics, Department of Human Molecular Genetics, Ihnestr. 73, D-14195 Berlin, GermanyMelanie Hambrock, Max Planck Institute for Molecular Genetics, Department of Human Molecular Genetics, Ihnestr. 73, D-14195 Berlin, GermanyUte Fischer, Max Planck Institute for Molecular Genetics, Department of Human Molecular Genetics, Ihnestr. 73, D-14195 Berlin, GermanyBettina Moser, Max Planck Institute for Molecular Genetics, Department of Human Molecular Genetics, Ihnestr. 73, D-14195 Berlin, GermanyBerten Ceulemans, Department of Neurology-Child Neurology, University of Antwerp, Antwerp, BelgiumWolfgang Lieb, Institut für Humangenetik, Universität zu Lübeck, Lübeck, ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4488044 Fri, 11 Feb 2011 11:51:02 +0100 4488044 A high-penetrance form of late-onset torsion dystonia maps to a novel locus (DYT21) on chromosome 2q14.3-q21.3 http://www.medworm.com/index.php?rid=4458741&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F153q713667361l86%2F This report will hopefully result in the identification of additional dystonia families with linkage to the same locus, and thereby, refinement of the disease critical region. Content Type Journal ArticlePages 1-7DOI 10.1007/s10048-011-0274-9Authors Nina Norgren, Unit for Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, SwedenEmma Mattson, Department of Genetics and Pathology, Uppsala University, Uppsala, SwedenLars Forsgren, Clinical Neuroscience Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, SwedenMonica Holmberg, Medical and Clinical Genetics Unit, Dept. of Medical Biosciences, Umeå University, Umeå, Sweden Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4458741 Mon, 07 Feb 2011 22:18:28 +0100 4458741 C4ORF48, a gene from the Wolf-Hirschhorn syndrome critical region, encodes a putative neuropeptide and is expressed during neocortex and cerebellar development http://www.medworm.com/index.php?rid=4441537&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftw6480445q321631%2F Abstract  In order to identify novel genes involved in mental retardation/intellectual disability, we focused on a microdeletion reported in a patient with a mild form of Wolf-Hirschhorn syndrome. This patient presented with attention-deficit hyperactivity disorder, some learning and fine motor deficits as well as facial abnormalities. The deleted region included three genes. Here, we report the first characterization of one of these genes, C4ORF48. C4ORF48 encodes a short (139 aa) evolutionarily conserved protein with a predicted signal peptide and two potential dibasic convertase cleavage sites. In mice, we demonstrated expression of the corresponding protein exclusively in brain tissue using an anti-mouse C4Orf48 polyclonal antibody. Detailed RNA in situ hybridization exp... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4441537 Thu, 03 Feb 2011 07:23:47 +0100 4441537 New clinical findings in the fragile X-associated tremor ataxia syndrome (FXTAS) http://www.medworm.com/index.php?rid=4427941&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr5158n1843u12423%2F We report on the first 50 subjects who have completed a full neurologic evaluation and a brain MRI. Subjects were selected on the basis of motor symptoms or abnormal results (>1 SD) on a quantitative instrument designed to detect mild tremor and ataxia (CATSYS 1994). A neuropsychological battery included the WAIS-III, COWA, and WCST. Statistical analysis used ANOVA and Fisher’s exact test with p < 0.05. All FMR1 premutation carriers were men of mean age 65 ± 7 years. According to the diagnostic criteria of Jacquemont et al. (Am J Hum Genet 72(4):869–878, 2003), 21 subjects met criteria for definite FXTAS, 10 for probable, 9 for possible, and 10 were indeterminate. Duration of motor symptoms was significantly longer in the definitive group (8.6 ± 6) compare... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4427941 Fri, 28 Jan 2011 20:32:23 +0100 4427941 Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1 http://www.medworm.com/index.php?rid=4410494&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7514242u62324775%2F Abstract  Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive neurodegenerative disorder characterized by retinitis pigmentosa and sensory ataxia. Previous studies of PCARP in two families showed a linkage to 1q31–q32. However, detailed investigations on the clinical presentations as well as molecular genetics of PCARP have been limited. Here, we describe a Japanese consanguineous family with PCARP. Two affected siblings suffered from childhood-onset retinitis pigmentosa and slowly progressive sensory ataxia. They also showed mild mental retardation, which has not been described in patients with PCARP. Parametric linkage analysis using high-density single nucleotide polymorphism arrays supported a linkage to the same locus. Target capture a... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4410494 Tue, 25 Jan 2011 23:34:59 +0100 4410494 Investigating the genetics of visual processing, function and behaviour in zebrafish http://www.medworm.com/index.php?rid=4410495&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn7757294mv07k234%2F Abstract  Over the past three decades, the zebrafish has been proven to be an excellent model to investigate the genetic control of vertebrate embryonic development, and it is now also increasingly used to study behaviour and adult physiology. Moreover, mutagenesis approaches have resulted in large collections of mutants with phenotypes that resemble human pathologies, suggesting that these lines can be used to model diseases and screen drug candidates. With the recent development of new methods for gene targeting and manipulating or monitoring gene expression, the range of genetic modifications now possible in zebrafish is increasing rapidly. Combined with the classical strengths of the zebrafish as a model organism, these advances are set to substantially expand the type ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4410495 Tue, 25 Jan 2011 23:34:56 +0100 4410495 Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms http://www.medworm.com/index.php?rid=4341763&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F176027841j7306jt%2F Abstract  Adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms features micturition urgency, constipation, erectile dysfunction, and orthostatic hypotension, usually followed by pyramidal signs and ataxia. Peripheral nerve conduction is normal. The disease is often mistaken for multiple sclerosis in the initial phase. There is a characteristic pattern of white matter changes in the brain and spinal cord on magnetic resonance imaging (MRI), mild atrophy of the brain, and a more marked atrophy of the spinal cord. ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplicat... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4341763 Tue, 11 Jan 2011 17:51:32 +0100 4341763 Progressive cavitating leukoencephalopathy associated with respiratory chain complex I deficiency and a novel mutation in NDUFS1 http://www.medworm.com/index.php?rid=4312831&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkl7712n8837k2543%2F We present clinical, neuroimaging, and molecular data on the identification of a new homozygous c.1783A>G (p.Thr595Ala) mutation in NDUFS1 in two inbred siblings with isolated complex I deficiency associated to a progressive cavitating leukoencephalopathy, a clinical and neuroradiological entity originally related to unknown defects of the mitochondrial energy metabolism. In both sibs, the muscle biopsy showed severe reduction of complex I enzyme activity, which was not obvious in fibroblasts. We also observed complex I dysfunction in a Neurospora crassa model of the disease, obtained by insertional mutagenesis, and in patient fibroblasts grown in galactose. Altogether, these results indicate that the NDUFS1 mutation is responsible for the disease and complex I deficiency. Clinical... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4312831 Mon, 03 Jan 2011 18:03:05 +0100 4312831 Inheritance of Charcot–Marie–Tooth disease 1A with rare nonrecurrent genomic rearrangement http://www.medworm.com/index.php?rid=4302786&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3812p05316457084%2F Abstract  Rare copy number variations by the nonrecurrent rearrangements involving PMP22 have been recently suggested to be associated with CMT1A peripheral neuropathy. As a mechanism of the nonrecurrent rearrangement, replication-based fork stalling template switching (FoSTeS) by microhomology-mediated break-induced replication (MMBIR) has been proposed. We found three Korean CMT1A families with putative nonrecurrent duplication. The duplications were identified by microsatellite typing and applying a CGH microarray. The breakpoint sequences in two families suggested an Alu–Alu-mediated rearrangement with the FoSTeS by the MMBIR, and a two-step rearrangement of the replication-based FoSTeS/MMBIR and meiosis-based recombination. The two-step mechanism has still not been rep... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4302786 Thu, 30 Dec 2010 18:03:54 +0100 4302786 Hydroxyurea enhances SMN2 gene expression through nitric oxide release http://www.medworm.com/index.php?rid=4283998&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2xm531r55083h17%2F Abstract  Small molecules that increase full-length survivor motor neuron (SMN) gene transcript are promising therapeutic candidates for spinal muscular atrophy (SMA). Hydroxyurea (HU) has recently been shown to increase full-length SMN transcript in cultured lymphocytes from patients with SMA. We investigate the mechanism by which HU enhances full-length SMN2 gene expression in SMA lymphocytes. Nitric oxide (NO) is a major intracellular metabolite of HU. We test whether NO donors can themselves enhance full-length SMN2 expression. Eighteen cell lines (five type I, five type II, six type III SMA, and two non-SMA controls) were treated with or without NO donors for 48 h. SMA cells treated with HU and three NO donors: two long-acting donors, Deta-NONOate and S-nitrosoglu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4283998 Tue, 21 Dec 2010 07:19:23 +0100 4283998 Screening of the THAP1 gene in patients with early-onset dystonia: myoclonic jerks are part of the dystonia 6 phenotype http://www.medworm.com/index.php?rid=4207008&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F60g0550h55g61201%2F Content Type Journal ArticleDOI 10.1007/s10048-010-0264-3Authors Fabienne Clot, Département de Génétique et Cytogénétique, AP-HP, Groupe Hospitalier Pitié Salpêtrière, Paris, FranceDavid Grabli, Fédération des Maladies du Système Nerveux, AP-HP, Groupe Hospitalier Pitié Salpêtrière, Paris, FrancePierre Burbaud, Service de Neurophysiologie Clinique, CHU de Bordeaux, Pessac, Bordeaux, FranceMagali Aya, Service de Neurologie, CHU de Grenoble, Grenoble, FrancePascal Derkinderen, INSERM, CIC0004, CHU Nantes, Nantes, FranceLuc Defebvre, Service de Neurologie, CNRS FRE 3291, CHU de Lille, Lille, FrancePhilippe Damier, INSERM, CIC0004, CHU Nantes, Nantes, FrancePierre Krystkowiak, Service de Neurologie, CNRS FRE 3291, CHU d’Amiens, Amiens, FrancePierre Pollak, Service de Neurol... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4207008 Thu, 25 Nov 2010 20:06:52 +0100 4207008 The effect of SNCA 3′ region on the levels of SNCA-112 splicing variant http://www.medworm.com/index.php?rid=4131233&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1h28076pl242t1p4%2F Abstract  Genetic variability at the 3′ region of SNCA locus has been repeatedly associated with susceptibility to sporadic Parkinson’s disease (PD). Accumulated evidence emphasizes the importance of SNCA dosage and expression levels in PD pathogenesis. However, the mechanism through which the 3′ region of SNCA gene modulates the risk to develop sporadic PD remained elusive. We studied the effect of PD risk-associated variants at SNCA 3′ regions on SNCA112-mRNA (exon 5 in-frame skipping) levels in vivo in 117 neuropathologically normal, human brain frontal cortex samples. SNPs tagging the SNCA 3′ showed significant effects on the relative levels of SNCA112-mRNA from total SNCA transcripts levels. The “risk” alleles were correlated with increased expression ratio ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=4131233 Tue, 02 Nov 2010 17:21:00 +0100 4131233 Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3 http://www.medworm.com/index.php?rid=3997034&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb654175168183788%2F Abstract  Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival. Content Type Journal ArticleDOI 10.1007/s1004... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3997034 Wed, 22 Sep 2010 16:42:51 +0100 3997034 Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family http://www.medworm.com/index.php?rid=3997035&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd87437661v732711%2F Abstract  Spastic paraplegia type 4 (SPG4) is the most common autosomal dominant hereditary SPG caused by mutations in the SPAST gene. We studied the four-generation pedigree of a Japanese family with autosomal dominant hereditary SPG both clinically and genetically. Twelve available family members (ten affected; two unaffected) and two spouses were enrolled in the study. The clinical features were hyperreflexia in all four limbs, spasticity of the lower extremities, impaired vibration sense, mild cognitive impairment confirmed by the Wechsler Adult Intelligence Scale—Third Edition, and peripheral neuropathy confirmed by neurophysiological examinations. All four female patients experienced miscarriages. The cerebrospinal fluid tau levels were mildly increased in two of thr... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3997035 Tue, 21 Sep 2010 11:23:03 +0100 3997035 Acknowledgement to Referees 2009/2010 http://www.medworm.com/index.php?rid=3997036&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8x2413211u21k40r%2F Content Type Journal ArticleDOI 10.1007/s10048-010-0262-5 Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 Journal Volume Volume 11 Journal Issue Volume 11, Number 4 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3997036 Mon, 20 Sep 2010 19:52:40 +0100 3997036 Novel ATP13A2 (PARK9) homozygous mutation in a family with marked phenotype variability http://www.medworm.com/index.php?rid=3997037&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpv38509m67nj0w41%2F Abstract  Mutations in the ATP13A2 (PARK9) and FBXO7 (PARK15) genes are linked to different forms of autosomal recessive juvenile-onset neurodegenerative diseases with overlapping phenotypes, including levodopa-responsive parkinsonism, pyramidal disturbances, cognitive decline, and supranuclear gaze disturbance. However, the associated genotypes and phenotypes are poorly characterized due to the small number of patients described. Here, we report clinical, instrumental, and genetic findings in an Italian family with novel PARK9 and PARK15 mutations. The proband developed a severe progressive phenotype including juvenile-onset parkinsonism, pyramidal disturbances, cognitive decline, and oculomotor abnormalities. On the contrary, his brother only shows mild abnormalities (pyram... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3997037 Mon, 20 Sep 2010 05:49:24 +0100 3997037 Confirmed association between monoamine oxidase A molecular polymorphisms and Sudden Infant Death Syndrome http://www.medworm.com/index.php?rid=3950037&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm08053850102u306%2F Content Type Journal ArticleDOI 10.1007/s10048-010-0257-2Authors Laura Filonzi, Department of Evolutionary and Functional Biology, University of Parma, Viale G.P. Usberti 11, 43100 Parma, ItalyCinzia Magnani, Department of Gynecology, Obstetrics and Neonatology, University of Parma, Via Gramsci, 43100 Parma, ItalyFrancesco Nonnis Marzano, Department of Evolutionary and Functional Biology, University of Parma, Viale G.P. Usberti 11, 43100 Parma, Italy Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3950037 Tue, 07 Sep 2010 06:28:43 +0100 3950037 A novel CLN2/TPP1 mutation in a Chinese patient with late infantile neuronal ceroid lipofuscinosis http://www.medworm.com/index.php?rid=3950038&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F570168l3368wt6pq%2F Content Type Journal ArticleDOI 10.1007/s10048-010-0258-1Authors Yu-Liang Wang, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University, Chang-gang-dong road 250, Guangzhou, 510260 ChinaZhi-Yong Zeng, Pediatric Department, Buji People’s Hospital, Shenzhen, 518112 ChinaXing-Wang Song, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University, Chang-gang-dong road 250, Guangzhou, 510260 ChinaZhuo-Fang Hao, Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Chang-gang-dong road 250, Guangzhou, 510260 ChinaYi-Wu Sh... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3950038 Tue, 07 Sep 2010 06:28:41 +0100 3950038 A FOXG1 mutation in a boy with congenital variant of Rett syndrome http://www.medworm.com/index.php?rid=3898342&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F500j1k7536k02715%2F Abstract  Mutations in the FOXG1 gene have been shown to cause congenital variant of Rett syndrome. To date, point mutations have been reported only in female patients. We screened the entire coding region of the gene for mutations in 50 boys with congenital encephalopathy, postnatal microcephaly, and complex movement disorders, a clinical picture very similar to that described in girls with FOXG1 mutations. We found one boy carrying the de novo c.256_257dupC frameshift mutation. He presented the association of postnatal microcephaly, severe axial dystonia with severe feeding difficulties with protruding tongue movements during the first year of life that subsequently evolved into dyskinetic movement disorders with hand stereotypies. In contrast to his severe motor impairmen... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3898342 Mon, 23 Aug 2010 17:57:02 +0100 3898342 A whole-genome scan in a large family with leukodystrophy and oligodontia reveals linkage to 10q22 http://www.medworm.com/index.php?rid=3884219&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1kk05263716547xj%2F Abstract  Dentoleukoencephalopathies with autosomal recessive inheritance are very rare. Recently, a large inbred Syrian pedigree was reported with oligodontia in association with a degenerative neurologic condition characterized by progressive ataxia and pyramidal syndrome and abnormalities in the white matter and cortical atrophy. A whole-genome screening of this family using 382 microsatellite markers was completed, but no evidence was found of linkage to any chromosomal region. A genome-wide linkage analysis using the 260K single nucleotide polymorphism Affymetrix array was then undertaken and a maximum multipoint logarithm of the odds score of 5.66 (NPL score = 7.65) was detected on chromosome 10q22 region. This genomic interval contains 95 known genes including th... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3884219 Wed, 18 Aug 2010 17:41:19 +0100 3884219 OCT1 polymorphism is associated with response and survival time in anti-Parkinsonian drug users http://www.medworm.com/index.php?rid=3819948&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm515uwk41k362844%2F Abstract  Substrates for the Organic Cation Transporter 1, encoded by the SLC22A1 gene, are metformin, amantadine, pramipexole, and, possibly, levodopa. Recently, we identified that the rs622342 A > C polymorphism is associated with the HbA1c lowering effect in metformin users. In the Rotterdam Study, we associated this polymorphism with higher prescribed doses of all anti-Parkinsonian drugs. Between the first and fifth prescriptions for levodopa, for each minor rs622342 C allele, the prescribed doses were 0.34 defined daily dose higher (95% CI 0.064, 0.62; p = 0.017). The mortality ratio after start of levodopa therapy was 1.47 times higher (95% CI 1.01, 2.13; p = 0.045). Content Type Journal ArticleCategory SHORT COMMUNICATIONDOI 10.1007/s10048-010-0254-5Auth... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3819948 Mon, 02 Aug 2010 20:27:09 +0100 3819948 Identification of novel SNPs of ABCD1, ABCD2, ABCD3, and ABCD4 genes in patients with X-linked adrenoleukodystrophy (ALD) based on comprehensive resequencing and association studies with ALD phenotypes http://www.medworm.com/index.php?rid=3797560&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx643852w726247v4%2F This study showed that ABCD2, ABCD3, and ABCD4 are less likely the disease-modifying genes, necessitating further studies to identify genes modifying ALD phenotypes. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-010-0253-6Authors Takashi Matsukawa, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo, Bunkyo Tokyo 113-8655 JapanMuriel Asheuer, UMR Inserm 745, University Paris-Descartes, Hôpital Saint-Vincent de Paul Paris FranceYuji Takahashi, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo, Bunkyo Tokyo 113-8655 JapanJun Goto, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo, Bunkyo Tokyo 113-8655 JapanYasuyuki Suzuki, Gifu University Gifu ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3797560 Mon, 26 Jul 2010 22:11:26 +0100 3797560 Targeted disruption of the Mast syndrome gene SPG21 in mice impairs hind limb function and alters axon branching in cultured cortical neurons http://www.medworm.com/index.php?rid=3797559&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff2j40470623j3888%2F In this study, we generated SPG21−/− knockout mice by homologous recombination as a possible animal model for SPG21. Though SPG21−/− mice appeared normal at birth, within several months they developed gradually progressive hind limb dysfunction. Cerebral cortical neurons cultured from SPG21−/− mice exhibited significantly more axonal branching than neurons from wild-type animals, while comprehensive neuropathological analysis of SPG21−/− mice did not reveal definitive abnormalities. Since alterations in axon branching have been seen in neurons derived from animal models of other forms of HSP as well as motor neuron diseases, this may represent a common cellular pathogenic theme. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-010-0252-7Author... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3797559 Mon, 26 Jul 2010 22:11:26 +0100 3797559 Tremor–ataxia with central hypomyelination (TACH) leukodystrophy maps to chromosome 10q22.3–10q23.31 http://www.medworm.com/index.php?rid=3775416&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg5h1313665p45855%2F We describe an autosomal recessive childhood-onset leukodystrophy with ataxia and tremor mapping to a 12.6 Mb interval on chromosome 10q22.3–10q23.31. Identification of the mutated gene will allow precise diagnosis and genetic counseling and shed light on how its perturbed function leads to white matter abnormalities. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-010-0251-8Authors Geneviève Bernard, Neuromics Center for Excellence of Université de Montréal, CRCHUM Laboratoire de neurogénétique de la motricité 1560 Sherbrooke East Montreal Quebec H2L 4M1 CanadaIsabelle Thiffault, Neuromics Center for Excellence of Université de Montréal, CRCHUM Laboratoire de neurogénétique de la motricité 1560 Sherbrooke East Montreal Quebec H2L 4M1 Cana... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3775416 Fri, 16 Jul 2010 19:02:31 +0100 3775416 Efficient identification of novel mutations in patients with limb girdle muscular dystrophy http://www.medworm.com/index.php?rid=3749222&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg14504033m621768%2F Abstract  Limb girdle muscular dystrophy type 2 (LGMD2) is a genetically heterogeneous autosomal recessive disorder caused by mutations in 15 known genes. DNA sequencing of all candidate genes can be expensive and laborious, whereas a selective sequencing approach often fails to provide a molecular diagnosis. We aimed to efficiently identify pathogenic mutations via homozygosity mapping in a population in which the genetics of LGMD2 has not been well characterized. Thirteen consanguineous families containing a proband with LGMD2 were recruited from Saudi Arabia, and for 11 of these families, selected individuals were genotyped at 10,204 single nucleotide polymorphisms. Linkage analysis excluded all but one or two known genes in ten of 11 genotyped families, and haplotype co... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3749222 Mon, 12 Jul 2010 06:19:39 +0100 3749222 A new locus (SPG46) maps to 9p21.2-q21.12 in a Tunisian family with a complicated autosomal recessive hereditary spastic paraplegia with mental impairment and thin corpus callosum http://www.medworm.com/index.php?rid=3717388&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6m3721038171u036%2F Abstract  Hereditary spastic paraplegia (HSP) with thin corpus callosum (TCC) and mental impairment is a frequent subtype of complicated HSP, often inherited as an autosomal recessive (AR) trait. It is clear from molecular genetic analyses that there are several underlying causes of this syndrome, with at least six genetic loci identified to date. However, SPG11 and SPG15 are the two major genes for this entity. To map the responsible gene in a large AR-HSP-TCC family of Tunisian origin, we investigated a consanguineous family with a diagnosis of AR-HSP-TCC excluded for linkage to the SPG7, SPG11, SPG15, SPG18, SPG21, and SPG32 loci. A genome-wide scan was undertaken using 6,090 SNP markers covering all chromosomes. The phenotypic presentation in five patients was suggestive ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3717388 Wed, 30 Jun 2010 15:21:27 +0100 3717388 GJB1/Connexin 32 whole gene deletions in patients with X-linked Charcot–Marie–Tooth disease http://www.medworm.com/index.php?rid=3654972&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw834p420231l8h74%2F Abstract  The X-linked form of Charcot–Marie–Tooth disease (CMTX) is the second most common form of this genetically heterogeneous inherited peripheral neuropathy. CMT1X is caused by mutations in the GJB1 gene. Most of the mutations causative for CMT1X are missense mutations. In addition, a few disease causative nonsense mutations and frameshift deletions that lead to truncated forms of the protein have also been reported to be associated with CMT1X. Previously, there have been reports of patients with deletions of the coding sequence of GJB1; however, the size and breakpoints of these deletions were not assessed. Here, we report five patients with deletions that range in size from 12.2 to 48.3 kb and that completely eliminate the entire coding sequence of the GJB1 g... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3654972 Wed, 09 Jun 2010 09:08:58 +0100 3654972 Age at onset in Huntington’s disease: replication study on the associations of ADORA2A, HAP1 and OGG1 http://www.medworm.com/index.php?rid=3628458&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkv7x7u3785628205%2F Abstract  In previous candidate gene studies, associations of the age at onset (AO) in Huntington disease (HD) have been reported with genetic variations in the genes encoding adenosinergic A2A receptor (ADORA2A), human huntingtin-associated protein-1 (HAP1) and the single base excision repair enzyme, 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1). Here, we sought to replicate these associations in an established study population of 419 unrelated German HD patients. AO was defined as the age at which the first motor signs of HD appeared, motor AO (mAO). For 215 patients, also information about the first behavioural or cognitive signs of HD was available, so that we also tested for an association with the earliest AO. No association was found with OGG1. For HAP1, we found mod... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3628458 Sat, 29 May 2010 16:54:12 +0100 3628458 Myotonic dystrophy type I combined with X-linked dominant Charcot–Marie–Tooth neuropathy http://www.medworm.com/index.php?rid=3541348&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F01h0825507w37x76%2F Abstract  Both the myotonic dystrophy type 1 (DM1) and the X-linked dominant Charcot–Marie–Tooth disease (CMTX1) are well-established inherited neuromuscular disorders characterized by progressive weakness and atrophy of the distal limb muscles. The underlying causes of the DM1 and CMTX1 are mutations in the DMPK and GJB1 gene, respectively. A patient with both DM1 and CMTX1 inherited these from his father and mother, respectively. Histopathological and electrodiagnostic studies revealed both chronic neuropathic and myopathic features. Physical disabilities were more severe than seen with either DM1 or CMTX1 alone. In addition, the present case reveals an asymmetric atrophy (22%) of the right calf muscle compared to the left side. Content Type Journal ArticleCategor... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3541348 Wed, 05 May 2010 08:12:33 +0100 3541348 Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred http://www.medworm.com/index.php?rid=3532798&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd0620hru61572425%2F In conclusion, we provide strong evidence for linkage of TS spectrum to chromosome 14q31.1. Suggestive linkage to an overlapping region of chromosome 14q was reported in a recent scan of TS sibling pairs. This region might therefore contain an important gene for TS, and it should be prioritized for further study. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-010-0244-7Authors Guido J. Breedveld, Erasmus MC Department of Clinical Genetics P.O. Box 2040 3000 CA Rotterdam The NetherlandsGiovanni Fabbrini, Sapienza University of Rome Department of Neurological Sciences and Neuromed Institute Rome ItalyBen A. Oostra, Erasmus MC Department of Clinical Genetics P.O. Box 2040 3000 CA Rotterdam The NetherlandsAlfredo Berardelli, Sapienza University of Rome Depa... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3532798 Sun, 02 May 2010 05:53:29 +0100 3532798 Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan http://www.medworm.com/index.php?rid=3518257&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg38032315284224k%2F Abstract  Spinocerebellar ataxia type 31 (SCA31) is a recently defined subtype of autosomal dominant cerebellar ataxia (ADCA) characterized by adult-onset, pure cerebellar ataxia. The C/T substitution in the 5′-untranslated region of the puratrophin-1 gene (PLEKHG4) or a disease-specific haplotype within the 900-kb SCA31 critical region just upstream of PLEKHG4 has been used for the diagnosis of SCA31. Very recently, a disease-specific insertion containing penta-nucleotide (TGGAA)n repeats has been found in this critical region in SCA31 patients. SCA31 was highly prevalent in Nagano, Japan, where SCA31 accounts for approximately 42% of ADCA families. We screened the insertion in 94 SCA31 patients from 71 families in Nagano. All patients had a 2.6- to 3.7-kb insertion. The si... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3518257 Wed, 28 Apr 2010 08:03:15 +0100 3518257 Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish http://www.medworm.com/index.php?rid=3479014&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj4771m862h72m646%2F This study represents the first investigation in zebrafish addressing the function of a causative gene in autosomal recessive HSP and identifies a critical role for spatacsin during early neural development in vivo. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-010-0243-8Authors Laura Southgate, School of Medicine, Floor 8 Tower Wing, Guy’s Hospital Department of Medical and Molecular Genetics, King’s College London London SE1 9RT UKDimitra Dafou, School of Medicine, Floor 8 Tower Wing, Guy’s Hospital Department of Medical and Molecular Genetics, King’s College London London SE1 9RT UKJacqueline Hoyle, School of Medicine, Floor 8 Tower Wing, Guy’s Hospital Department of Medical and Molecular Genetics, King’s College London London SE1 9RT UKNan... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3479014 Tue, 13 Apr 2010 18:16:10 +0100 3479014 LINGO1 and LINGO2 variants are associated with essential tremor and Parkinson disease http://www.medworm.com/index.php?rid=3452573&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw718576187168k32%2F Abstract  Genetic variation in the leucine-rich repeat and Ig domain containing 1 gene (LINGO1) was recently associated with an increased risk of developing essential tremor (ET) and Parkinson disease (PD). Herein, we performed a comprehensive study of LINGO1 and its paralog LINGO2 in ET and PD by sequencing both genes in patients (ET, n = 95; PD, n = 96) and by examining haplotype-tagging single-nucleotide polymorphisms (tSNPs) in a multicenter North American series of patients (ET, n = 1,247; PD, n = 633) and controls (n = 642). The sequencing study identified six novel coding variants in LINGO1 (p.S4C, p.V107M, p.A277T, p.R423R, p.G537A, p.D610D) and three in LINGO2 (p.D135D, p.P217P, p.V565V), however segregation analysis did not support pathogenicity. T... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3452573 Mon, 05 Apr 2010 21:34:04 +0100 3452573 Analysis of NF1 somatic mutations in cutaneous neurofibromas from patients with high tumor burden http://www.medworm.com/index.php?rid=3432048&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0001q42468251877%2F Abstract  Neurofibromatosis type 1, (NF1) is a complex, autosomal dominant disorder characterized by benign and malignant tumors which result from NF1 gene mutations. The molecular mechanisms that underlie NF1 tumorigenesis are still poorly understood although inactivation of other modifying loci in conjunction with NF1 mutations is postulated to be involved. These modifying loci may include deficiencies in mismatch repair genes and elements involved in cell cycle regulation (TP53, RB1, and CDKN2A). We have analyzed the somatic mutations in 89 cutaneous neurofibromas derived from three unrelated NF1 patients with high tumor burden, by loss of heterozygosity (LOH) analysis of the NF1, TP53, RB1, and CDKN2A genes, by assessing microsatellite instability (MSI), by direct sequenc... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3432048 Wed, 31 Mar 2010 17:00:44 +0100 3432048 Questionable association between a monoamine oxidase A promoter polymorphism and sudden infant death syndrome http://www.medworm.com/index.php?rid=3432049&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5g778p1543v137m7%2F Content Type Journal ArticleCategory LETTER TO THE EDITORSDOI 10.1007/s10048-010-0242-9Authors Michael Klintschar, Hannover Medical School Institute of Legal Medicine Hannover GermanyChristian Heimbold, University Göttingen Institute of Legal Medicine Göttingen Germany Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3432049 Wed, 31 Mar 2010 05:42:53 +0100 3432049 RNA processing pathways in amyotrophic lateral sclerosis http://www.medworm.com/index.php?rid=3412331&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fdh71746657470471%2F Abstract  RNA processing is a tightly regulated, highly complex pathway which includes RNA transcription, pre-mRNA splicing, editing, transportation, translation, and degradation of RNA. Over the past few years, several RNA processing genes have been shown to be mutated or genetically associated with amyotrophic lateral sclerosis (ALS), including the RNA-binding proteins TDP-43 and FUS/TLS. These findings suggest that RNA processing may represent a common pathogenic mechanism involved in development of ALS. In this review, we will discuss six ALS-related, RNA processing genes including their discovery, function, and commonalities. Content Type Journal ArticleCategory REVIEW ARTICLEDOI 10.1007/s10048-010-0239-4Authors Marka van Blitterswijk, University of Massachusetts ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3412331 Fri, 26 Mar 2010 19:19:45 +0100 3412331 Molecular characterization of six Chinese families with m.3460G>A and Leber hereditary optic neuropathy http://www.medworm.com/index.php?rid=3372925&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx733645258725278%2F Abstract  The primary mutation m.3460G>A occurs with a very low frequency (∼1%) in Chinese patients with Leber hereditary optic neuropathy (LHON). Up to now, there is no comprehensive study of Chinese patients harboring this mutation. We characterized six unrelated probands with m.3460G>A in this study, which were identified from 1,626 patients with LHON or suspected with LHON. The overall penetrance of LHON (25.6% [10/39]) in four pedigrees with m.3460G>A was substantially lower than those families with m.11778G>A (33.3% [619/1859]) as reported in our previous study. Intriguingly, family Le688 with a heteroplasmic m.3460G>A presented a lower penetrance (12.5%) than the other three families with a homoplasmic mutation. There is an elevated gender bias (affec... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3372925 Mon, 15 Mar 2010 17:56:12 +0100 3372925 L239F founder mutation in GDAP1 is associated with a mild Charcot–Marie–Tooth type 4C4 (CMT4C4) phenotype http://www.medworm.com/index.php?rid=3372926&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63u5261608600754%2F In this study, we identified the L239F mutation in the GDAP1 gene in one Bulgarian and five Polish families. We hypothesized that the L239F mutation may result from a founder effect in the European population since this mutation has previously been reported in Belgian, Czech, and Polish patients. In fact, we detected a common disease-associated haplotype within the 8q13-q21 region in the Polish, German, Italian, Czech, and Bulgarian CMT families. Like the previously detected “regional” S194X and Q163X mutations, respectively present in Maghreb countries and in patients of Spanish descent, the L239F mutation seems to be the most common GDAP1 pathogenic variant in the Central and Eastern European population. Given the likely presence of a common ancestor harboring the L239F mutatio... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3372926 Mon, 15 Mar 2010 17:56:11 +0100 3372926 X-linked CMT: genes and gene loci in an Australian cohort http://www.medworm.com/index.php?rid=3357673&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr5l31046132h384j%2F Content Type Journal ArticleCategory LETTER TO THE EDITORSDOI 10.1007/s10048-010-0238-5Authors Megan Hwa Brewer, ANZAC Research Institute Northcott Neuroscience Laboratory Concord New South Wales Australia 2139Rabia Chaudhry, ANZAC Research Institute Northcott Neuroscience Laboratory Concord New South Wales Australia 2139Keta McDowall, University of Sydney Faculty of Medicine Camperdown New South Wales AustraliaShannon Chu, ANZAC Research Institute Northcott Neuroscience Laboratory Concord New South Wales Australia 2139Bartosz Kowalski, ANZAC Research Institute Northcott Neuroscience Laboratory Concord New South Wales Australia 2139Patsie Polly, ANZAC Research Institute Cancer Pharmacology Unit Concord New South Wales AustraliaGarth Nicholson, ANZAC Research Institute Northcott Neurosc... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3357673 Wed, 10 Mar 2010 15:44:12 +0100 3357673 Meta-analysis of association between variation in the PDE4D gene and ischemic cerebral infarction risk in Asian populations http://www.medworm.com/index.php?rid=3313914&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fhv880441wv05613w%2F Abstract  Phosphodiesterase 4D (PDE4D) was found to be associated with increased risk of ischemic stroke by Iceland researchers in 2003. Replication studies have produced conflicting results. A recent meta-analysis reported that no genetic variant of PDE4D demonstrated a reproducible association with ischemic stroke, especially when analyzed with respect to white subjects exclusively. In this study, we aimed to determine the association between PDE4D and ischemic infarction risk in Asian populations. After collecting all case–control studies in English or Chinese related to the association between PDE4D and ischemic infarction in Asian people, strict selection criteria and exclusion criteria were determined, and a fixed or random effects model was used on the basis of het... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3313914 Thu, 25 Feb 2010 06:54:26 +0100 3313914 Fine mapping of the chromosome 10q11-q21 linkage region in Alzheimer's disease cases and controls http://www.medworm.com/index.php?rid=3313915&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F127124845x5m4qp3%2F Abstract  We have previously reported strong linkage on chromosome 10q in pedigrees transmitting Alzheimer's disease through the mother, overlapping with many significant linkage reports including the largest reported study. Here, we report the most comprehensive fine mapping of this region to date. In a sample of 638 late-onset Alzheimer's disease (LOAD) cases and controls including 104 maternal LOAD cases, we genotyped 3,884 single nucleotide polymorphisms (SNPs) covering 15.2 Mb. We then used imputations and publicly available data to generate an extended dataset including 4,329 SNPs for 1,209 AD cases and 839 controls in the same region. Further, we screened eight genes in this region for rare alleles in 283 individuals by nucleotide sequencing, and we tested for p... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3313915 Thu, 25 Feb 2010 06:54:24 +0100 3313915 Atypical, perhaps under-recognized? An unusual phenotype of Friedreich ataxia http://www.medworm.com/index.php?rid=3282715&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1217270542756517%2F We describe here a 41-year-old man with profound vision deficit and episodic complete blindness associated with marked optic atrophy, spastic paraparesis, and sensory neuropathy without ataxia whose diagnostic evaluation revealed compound heterozygosity for two frataxin mutations, a 994 GAA repeat intronic expansion and c.389G > T (p.G130V) missense mutation. This case emphasizes that FRDA should be considered for individuals with significant vision deficit with optic atrophy and sensory neuropathy, even in the absence of ataxia. This case also raises the additional, related concern that prior studies may underestimate the frequency and varieties of variant forms of FRDA. Content Type Journal ArticleCategory SHORT COMMUNICATIONDOI 10.1007/s10048-009-0233-xAuthors Beate D... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3282715 Tue, 16 Feb 2010 18:06:44 +0100 3282715 Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy http://www.medworm.com/index.php?rid=3192547&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg1n0748538h2h755%2F We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0232-yAuthors Luis E. Kolb, Program on Neurogenetics Yale University School of Medicine Department of Neurosurgery, Neurobiology New Haven ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3192547 Fri, 15 Jan 2010 18:00:13 +0100 3192547 Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19 http://www.medworm.com/index.php?rid=3128358&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F527247x01800567x%2F Abstract  We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0230-0Authors K. G. Meilleur, National Institutes of Health Neurogenetics Branch, National Institute of Neurological Disorders and Stroke Bethesda MD USAM. Traoré, P... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3128358 Mon, 28 Dec 2009 19:19:41 +0100 3128358 The C15orf2 gene in the Prader–Willi syndrome region is subject to genomic imprinting and positive selection http://www.medworm.com/index.php?rid=3106547&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjh08tm752gk8l88v%2F Abstract   C15orf2 (Chromosome 15 open reading frame 2) is an intronless gene, which is located in the Prader–Willi syndrome (PWS) chromosomal region on human chromosome 15. Mice do not have an orthologous gene. Here we show that expression of C15orf2 in the fetal human brain is imprinted. Using Western blot and immunohistological studies we have obtained evidence that C15orf2 protein is present in several regions of the brain. Previously published phylogenetic studies as well as population genetic studies based on complex haplotypes as described here suggest that C15orf2 is under positive Darwinian selection. These results indicate that C15orf2 might have an important role in human biology and that a deficiency of C15orf2 might contribute to PWS. Content Type Journal A... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3106547 Fri, 18 Dec 2009 07:07:22 +0100 3106547 Analysis of exon dosage using MLPA in South African Parkinson's disease patients http://www.medworm.com/index.php?rid=3099411&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fju165081744w314m%2F Abstract  Genomic rearrangements (exon dosage) are common mutations reported in Parkinson's disease (PD) patients. In the present study, we aimed to investigate the prevalence of genomic rearrangements in 88 South African patients with predominantly early-onset PD (age-at-onset ≤50 years). The multiplex ligation-dependent probe amplification method was used to detect exon dosage changes. Two commercially available probe kits, SALSA P051 and P052, were used and together the kits consisted of probes for exons of α-synuclein, parkin, PINK1, DJ-1, LRRK2, UCH-L1, ATP13A2, LPA, TNFRSF9, CAV2, CAV1, GCH1, and two-point mutations. We identified exonic rearrangements in parkin and α-synuclein in 8% of South African patients from different ethnic groups. One patient had a whol... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3099411 Tue, 15 Dec 2009 06:49:19 +0100 3099411 Evidence against haploinsuffiency of human ataxin 10 as a cause of spinocerebellar ataxia type 10 http://www.medworm.com/index.php?rid=3016824&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F37422x4278157338%2F Content Type Journal ArticleCategory LETTERDOI 10.1007/s10048-009-0227-8Authors Boris Keren, GH Pitié-Salpêtrière, AP-HP Département de Génétique et Cytogénétique, CGMC Paris FranceAurélia Jacquette, GH Pitié-Salpêtrière, AP-HP Département de Génétique et Cytogénétique, CGMC Paris FranceChristel Depienne, GH Pitié-Salpêtrière, AP-HP Département de Génétique et Cytogénétique, CGMC Paris FrancePatricia Leite, GH Pitié-Salpêtrière, AP-HP Département de Génétique et Cytogénétique, CGMC Paris FranceAlexandra Durr, GH Pitié-Salpêtrière, AP-HP Département de Génétique et Cytogénétique, CGMC Paris FranceWassila Carpentier, Inserm, UPMC Paris 6, GH Pitié-Salpêtrière Plateforme Post-génomique de la Pitié-Salpêtrière Paris FranceBaya Benyahia, GH Pi... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3016824 Thu, 19 Nov 2009 20:01:05 +0100 3016824 Novel variants identified in methyl-CpG-binding domain genes in autistic individuals http://www.medworm.com/index.php?rid=3011264&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk089753tr5150g4q%2F Abstract  Misregulation of the methyl-CpG-binding protein 2 (MECP2) gene has been found to cause a myriad of neurological disorders including autism, mental retardation, seizures, learning disabilities, and Rett syndrome. We hypothesized that mutations in other members of the methyl-CpG-binding domain (MBD) family may also cause autistic features in individuals. We evaluated 226 autistic individuals for alterations in the four genes most homologous to MECP2: MBD1, MBD2, MBD3, and MBD4. A total of 46 alterations were identified in the four genes, including ten missense changes and two deletions that alter coding sequence. Several are either unique to our autistic population or cosegregate with affected individuals within a family, suggesting a possible relation of these varia... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3011264 Tue, 17 Nov 2009 23:48:49 +0100 3011264 Atp10a, a gene adjacent to the PWS/AS gene cluster, is not imprinted in mouse and is insensitive to the PWS-IC http://www.medworm.com/index.php?rid=2971749&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fvt740kr084370875%2F We report that Atp10a is biallelically expressed in both the newborn and adult brain, and Atp10a allelic expression is insensitive to deletion or mutation of the PWS imprinting center. The CpG island associated with Atp10a is hypomethylated, a result consistent with the notion that Atp10a is not an imprinted gene. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0226-9Authors Amanda J. DuBose, University of Florida College of Medicine Department of Molecular Genetics and Microbiology Gainesville Florida 32610-0266 USAKaren A. Johnstone, Peninsula Medical School, University of Exeter Institute of Biomedical and Clinical Sciences Exeter EX2 5DW UKEmily Y. Smith, University of Florida College of Medicine Department of Molecular Genetics and Microbiology Gainesv... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2971749 Thu, 05 Nov 2009 18:57:51 +0100 2971749 Isolated eyelid closure myotonia in two families with sodium channel myotonia http://www.medworm.com/index.php?rid=2948157&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1690r243321755w7%2F We describe the first distinctive clinical genotype–phenotype correlation within NaCh: a strictly isolated eyelid closure myotonia associated with the L250P mutation in SCN4A. Using clinical assessment and needle EMG, we identified this genotype–phenotype correlation in six L250P patients from one NaCh family and confirmed this finding in another, unrelated NaCh family with three L250P patients. Content Type Journal ArticleCategory SHORT COMMUNICATIONDOI 10.1007/s10048-009-0225-xAuthors B. C. Stunnenberg, Radboud University Nijmegen Medical Centre Department of Neurology, Neuromuscular Centre Nijmegen Reinier Postlaan 4 PO-box 9101 6500 HB Nijmegen The NetherlandsH. B. Ginjaar, Leiden University Medical Centre Department of Human and Clinical Genetics Leiden The NetherlandsJ. T... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2948157 Thu, 29 Oct 2009 19:39:45 +0100 2948157 Suggestive evidence on chromosomes 2 and 19 for HTR1A-independent linkage of genes to major depression http://www.medworm.com/index.php?rid=2878567&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F762n5644x462n410%2F Content Type Journal ArticleCategory LETTERDOI 10.1007/s10048-009-0222-0Authors Victor Abkevich, Myriad Genetics 320 Wakara Way Salt Lake City UT 84108 USAChris D. Neff, Myriad Genetics 320 Wakara Way Salt Lake City UT 84108 USAJennifer Potter, Myriad Genetics 320 Wakara Way Salt Lake City UT 84108 USARobin Riley, Myriad Genetics 320 Wakara Way Salt Lake City UT 84108 USADonna Shattuck, Myriad Genetics 320 Wakara Way Salt Lake City UT 84108 USADavid A. Katz, Abbott Laboratories 100 Abbott Park Road, R48B/AP4 Abbott Park IL 60064 USA Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2878567 Thu, 08 Oct 2009 07:17:23 +0100 2878567 Revisiting the phenotype associated with FOXG1 mutations: two novel cases of congenital Rett variant http://www.medworm.com/index.php?rid=2870949&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F556g373404560632%2F Abstract  The Forkhead box G1 (FOXG1) is a transcription factor that is critical for forebrain development, where it promotes progenitor proliferation and suppresses premature neurogenesis. Recently, the FOXG1 gene was implicated in the molecular aetiology of the congenital variant of Rett syndrome. So far, 15 FOXG1 molecular alterations, including only eight point mutations, have been reported. We screened the FOXG1 gene in a cohort of 206 MECP2 and CDKL5 mutation negative patients (136 females and 70 males) with severe encephalopathy and microcephaly. The screening was negative in all males, but two de novo mutations (c.1248C>G, p.Y416X and c.460_461dupG, p.E154GfsX300) were identified in two unrelated girls. Both patients showed neurological symptoms from the neonatal pe... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2870949 Tue, 06 Oct 2009 12:46:54 +0100 2870949 Acknowledgement to Referees 2008/2009 http://www.medworm.com/index.php?rid=2857064&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm9k2ku12t824504x%2F Content Type Journal ArticleCategory ACKNOWLEDGEMENT TO REFEREESDOI 10.1007/s10048-009-0221-1 Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 Journal Volume Volume 10 Journal Issue Volume 10, Number 4 / October, 2009 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2857064 Wed, 30 Sep 2009 18:19:59 +0100 2857064 A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation http://www.medworm.com/index.php?rid=2854462&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F50272w661g7m4311%2F Abstract  We have identified a novel splice site mutation (IVS6-1G > A) in the disc-large homolog 3 (DLG3) gene, encoding the synapse-associated protein 102 (SAP102) in one out of 300 families with moderate to severe non-syndromic mental retardation. SAP102 is a member of the neuronal membrane-associated guanylate kinase protein subfamily comprising SAP97, postsynaptic density (PSD)95, and PSD93, which interacts with methyl-d-aspartate receptor and associated protein complexes at the postsynaptic density of excitatory synapses. DLG3 is the first mental retardation gene directly linked to glutamate receptor signalling and trafficking, increasingly recognised as a central mechanism in the regulation of synaptic formation and plasticity in brain and cognitive development. ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2854462 Wed, 30 Sep 2009 18:19:47 +0100 2854462 A Copine family member, Cpne8, is a candidate quantitative trait gene for prion disease incubation time in mouse http://www.medworm.com/index.php?rid=2854463&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F40g85668143xp6k5%2F In this study, we use the Northport heterogeneous stock of mice to reduce the size of a previously identified QTL on Mmu15 from approximately 25 to 1.2 cM. We further characterised the genes in this region and identify Cpne8, a member of the copine family, as the most promising candidate gene. We also show that Cpne8 mRNA is upregulated at the terminal stage of disease, supporting a role in prion disease. Applying these techniques to other loci will facilitate the identification of key pathways in prion disease pathogenesis. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0219-8Authors Sarah E. Lloyd, UCL Institute of Neurology MRC Prion Unit and Department of Neurodegenerative Diseases London WC1N 3BG UKEmma G. Maytham, UCL Institute of Neurology MR... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2854463 Wed, 30 Sep 2009 18:19:45 +0100 2854463 Progressive retinal atrophy in Schapendoes dogs: mutation of the newly identified CCDC66 gene http://www.medworm.com/index.php?rid=2835946&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff957817521381672%2F Abstract  Canine generalized progressive retinal atrophy (gPRA) is characterized by continuous degeneration of photoreceptor cells leading to night blindness and progressive vision loss. Until now, mutations in 11 genes have been described that account for gPRA in dogs, mostly following an autosomal recessive inheritance mode. Here, we describe a gPRA locus comprising the newly identified gene coiled-coil domain containing 66 (CCDC66) on canine chromosome 20, as identified via linkage analysis in the Schapendoes breed. Mutation screening of the CCDC66 gene revealed a 1-bp insertion in exon 6 leading to a stop codon as the underlying cause of disease. The insertion is present in all affected dogs in the homozygous state as well as in all obligatory mutation carriers in the het... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2835946 Thu, 24 Sep 2009 14:34:23 +0100 2835946 Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models http://www.medworm.com/index.php?rid=2811994&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmg6154150878011v%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10048-009-0213-1Authors Alejandro Leal, Friedrich-Alexander University Institute of Human Genetics Schwabachanlage 10 91054 Erlangen GermanyKathrin Huehne, Friedrich-Alexander University Institute of Human Genetics Schwabachanlage 10 91054 Erlangen GermanyFinn Bauer, Friedrich-Alexander University Institute of Biochemistry Emil-Fischer-Zentrum, Fahrstraße 17 91054 Erlangen GermanyHeinrich Sticht, Friedrich-Alexander University Institute of Biochemistry Emil-Fischer-Zentrum, Fahrstraße 17 91054 Erlangen GermanyPhilipp Berger, Swiss Federal Institute of Technology (ETH) HPM-II E39, Institute of Cell Biology, ETH Hönggerberg 8093 Zürich SwitzerlandUeli Suter, Swiss Federal Institute of Technology (ETH) HPM-II E39, Institute of C... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2811994 Thu, 17 Sep 2009 12:20:39 +0100 2811994 Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice http://www.medworm.com/index.php?rid=2811995&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F532nq762353t7707%2F Abstract  Synphilin-1 has been identified as an interacting protein of alpha-synuclein, Parkin, and LRRK2, proteins which are mutated in familial forms of Parkinson’s disease (PD). Subsequently, synphilin-1 has also been shown to be an intrinsic component of Lewy bodies in sporadic PD. In order to elucidate the role of synphilin-1 in the pathogenesis of PD, we generated transgenic mice overexpressing wild-type and mutant (R621C) synphilin-1 driven by a mouse prion protein promoter. Transgenic expression of both wild-type and the R621C variant synphilin-1 resulted in increased dopamine levels of the nigrostriatal system in 3-month-old mice. Furthermore, we found pathological ubiquitin-positive inclusions in cerebellar sections and dark-cell degeneration of Purkinje cells. ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2811995 Thu, 17 Sep 2009 12:20:38 +0100 2811995 Intratumoral patterns of clonal evolution in gliomas http://www.medworm.com/index.php?rid=2811996&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flh33285l51tu2007%2F Abstract  Few studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase—FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed ≥2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic p... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2811996 Thu, 17 Sep 2009 12:20:37 +0100 2811996 Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis http://www.medworm.com/index.php?rid=2811997&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4u42v73422v12484%2F Abstract  The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 F... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2811997 Thu, 17 Sep 2009 12:20:36 +0100 2811997 Periphilin is a novel interactor of synphilin-1, a protein implicated in Parkinson's disease http://www.medworm.com/index.php?rid=2811998&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk27762924793408k%2F Abstract  Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons and the presence of Lewy bodies. Alpha-synuclein and its interactor synphilin-1 are major components of these inclusions. Rare mutations in the α-synuclein and synphilin-1 genes have been implicated in the pathogenesis of PD; however, the normal function of these proteins is far from being completely elucidated. We, thus, searched for novel synphilin-1-interacting proteins and deciphered periphilin as new interactor. Periphilin isoforms are involved in multiple cellular functions in vivo, and the protein is broadly expressed during embryogenesis and in the adult brain. We show that periphilin displays an overlapping expression pattern with synphilin-1 ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2811998 Wed, 16 Sep 2009 19:00:45 +0100 2811998 Congenital bovine spinal dysmyelination is caused by a missense mutation in the SPAST gene http://www.medworm.com/index.php?rid=2745362&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftx85775k63772174%2F Abstract  Bovine spinal dysmyelination (BSD) is a recessive congenital neurodegenerative disease in cattle (Bos taurus) characterized by pathological changes of the myelin sheaths in the spinal cord. The occurrence of BSD is a longstanding problem in the American Brown Swiss (ABS) breed and in several European cattle breeds upgraded with ABS. Here, we show that the disease locus on bovine chromosome 11 harbors the SPAST gene that, when mutated, is responsible for the human disorder hereditary spastic paraplegia (HSP). Initially, SPAST encoding Spastin was considered a less likely candidate gene for BSD since the modes of inheritance as well as the time of onset and severity of symptoms differ widely between HSP and BSD. However, sequence analysis of the bovine SPAST gene in af... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2745362 Fri, 28 Aug 2009 16:59:29 +0100 2745362 Increased transcript diversity: novel splicing variants of Machado–Joseph Disease gene (ATXN3) http://www.medworm.com/index.php?rid=2745363&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj075w6108202210l%2F Abstract  Machado–Joseph disease (MJD) is a late-onset neurodegenerative disorder that presents clinical heterogeneity not completely explained by its causative mutation. MJD is caused by an expansion of a CAG tract at exon 10 of the ATXN3 gene (14q32.1), which encodes for ataxin-3. The main goal of this study was to analyze the occurrence of alternative splicing at the ATXN3 gene, by sequencing a total of 415 cDNAs clones (from 20 MJD patients and 14 controls). Two novel exons are described for the ATXN3 gene. Fifty-six alternative splicing variants, generated by four types of splicing events, were observed. From those variants, 50 were not previously described, and 26 were only found in MJD patients samples. Most of the variants (85.7%) present frameshift, which leads to... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2745363 Fri, 28 Aug 2009 16:59:28 +0100 2745363 Compound Charcot-Marie-Tooth disease may determine unusual and milder phenotypes http://www.medworm.com/index.php?rid=2733157&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa3225464j6632x1l%2F In this report, we present a father and a daughter with a very mild and unusual disease that segregates with two mutations in PMP22 gene, the 17p11.2-p12 duplication and a Ser72Leu point mutation. We propose that the deleterious effects of each mutation are partially compensated by the functional effect of the other. Content Type Journal ArticleCategory SHORT COMMUNICATIONDOI 10.1007/s10048-009-0211-3Authors Silmara P. Gouvea, University of São Paulo Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto São Paulo BrazilVinícius H. S. Borghetti, University of São Paulo Department of Neurosciences and Behavioral Sciences, School of Medicine of Ribeirão Preto São Paulo BrazilKeity C. Bueno, University of São Paulo Department of Neurosciences ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2733157 Mon, 24 Aug 2009 16:53:07 +0100 2733157 Prader–Willi syndrome, Snord115, and Htr2c editing http://www.medworm.com/index.php?rid=2681002&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe18627x506322848%2F Content Type Journal ArticleCategory LETTER TO THE EDITORSDOI 10.1007/s10048-009-0209-xAuthors Heather Glatt-Deeley, University of Connecticut School of Medicine Department of Genetics and Developmental Biology 263 Farmington Ave Farmington CT 06030-3301 USADaria L. Bancescu, University of Connecticut School of Medicine Department of Genetics and Developmental Biology 263 Farmington Ave Farmington CT 06030-3301 USAMarc Lalande, University of Connecticut School of Medicine Department of Genetics and Developmental Biology 263 Farmington Ave Farmington CT 06030-3301 USA Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2681002 Mon, 03 Aug 2009 20:46:51 +0100 2681002 Sequence variation in SORL1 and dementia risk in Swedes http://www.medworm.com/index.php?rid=2681003&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F613j446122624812%2F Abstract  The gene encoding the neuronal sortilin-related receptor SORL1 has been claimed to be associated with Alzheimer's disease (AD) by independent groups and across various human populations. We evaluated six genetic markers in SORL1 in a sample of 1,558 Swedish dementia cases (including 1,270 AD cases) and 2,179 controls. For both single-marker-based and haplotype-based analyses, we found no strong support for SORL1 as a dementia or AD risk-modifying gene in our sample in isolation nor did we observe association with AD/dementia-related traits, including cerebrospinal fluid β-amyloid1–42, tau levels, or age at onset. However, meta-analyses of markers in this study together with previously published studies on SORL1 encompassing in excess of 13,000 individuals does su... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2681003 Mon, 03 Aug 2009 20:46:49 +0100 2681003 Identification of CACNA1A large deletions in four patients with episodic ataxia http://www.medworm.com/index.php?rid=2644242&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F72r4g1721k054244%2F Abstract  Episodic ataxia is an autosomal dominant ion channel disorder characterized by paroxysmal attacks of incoordination. Episodic ataxia type 2 (EA2) is caused by mutations in CACNA1A. EA2 mutations are mostly nonsense and sometimes missense mutations. However, in some typical EA2 families, CACNA1A sequencing does not detect any point mutation. Herein, we have designed a quantitative multiplex polymerase chain reaction of short fluorescent fragment test to screen the 50 exons of CACNA1A and investigated 27 probands referred for molecular diagnosis of EA2 who did not show any point mutation in CACNA1A. We have identified four different exonic deletions in four patients with a typical EA2 phenotype. These results establish the need to complete sequencing analysis by a sc... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2644242 Sat, 25 Jul 2009 14:50:53 +0100 2644242 Adenine nucleotide translocase is involved in a mitochondrial coupling defect in MFN2-related Charcot–Marie–Tooth type 2A disease http://www.medworm.com/index.php?rid=2624764&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx672u43u451j8164%2F Abstract  Charcot–Marie–Tooth type 2A disease (CMT2A), a dominantly inherited peripheral neuropathy, is caused by mutations in MFN2, a mitochondrial fusion protein. Having previously demonstrated a mitochondrial coupling defect in CMT2A patients’ fibroblasts, we here investigate mitochondrial oxygen consumption and the expression of adenine nucleotide translocase (ANT) and uncoupling proteins from eight other patients with the disease. The mitochondrial uncoupling was associated with a higher respiratory rate, essentially involving complex II proteins. Furthermore, a twofold increase in the expression of ANT led to the reduced efficiency of oxidative phosphorylation in CMT2A cells, suggesting that MFN2 plays a role in controlling ATP/ADP exchanges. Content Type Journ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2624764 Sat, 18 Jul 2009 08:42:11 +0100 2624764 Characterization of two novel SETX mutations in AOA2 patients reveals aspects of the pathophysiological role of senataxin http://www.medworm.com/index.php?rid=2597261&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq5runj3124501651%2F Abstract  Ataxia with oculomotor apraxia (AOA) type 2 (AOA2 MIM 606002) is a recessive subtype of AOA characterized by cerebellar atrophy, oculomotor apraxia, early loss of reflexes, and peripheral neuropathy. Various mutations either in homozygous or compound heterozygous condition were so far identified in the associated gene SETX (MIM 608465). SETX encodes a large protein called senataxin with a DNA-RNA helicase domain and a putative N-terminus protein interaction domain. Here, we report the identification of two novel homozygous mutations in SETX gene, c.340_342delCTT (p.L114Del) and c.1669C > T (p.R557X), in two AOA2 families. The characterization of the mutant lymphoblastoid cell lines for sensitivity to oxidative DNA-damaging agents indicates that the p.L114Del ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2597261 Sat, 11 Jul 2009 06:47:27 +0100 2597261 Schwannomatosis associated with multiple meningiomas due to a familial SMARCB1 mutation http://www.medworm.com/index.php?rid=2590480&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0g16mu0527gk5ju7%2F We report a family with multiple schwannomas and meningiomas. A SMARCB1 germline mutation in exon 1 was identified. The mutation, c.92A>T (p.Glu31Val), occurs in a highly conserved amino acid in the SMARCB1 protein. In addition, in silico analysis demonstrated that the mutation disrupts the donor consensus sequence of exon 1. RNA studies verified the absence of mRNA transcribed by the mutant allele. This is the first report of a SMARCB1 germline mutation in a family with schwannomatosis characterized by the development of multiple meningiomas. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0204-2Authors Costanza Bacci, University of Florence Medical Genetics Unit, Department of Clinical Physiopathology Florence ItalyRoberta Sestini, University of Flor... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2590480 Tue, 07 Jul 2009 15:27:45 +0100 2590480 Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder http://www.medworm.com/index.php?rid=2590481&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyl886372552u6071%2F Abstract  Patients with autism spectrum disorder (ASD) frequently harbour chromosome rearrangements and segmental aneuploidies, which allow us to identify candidate genes. In a boy with mild facial dysmorphisms, speech delay and ASD, we reconstructed by karyotyping, FISH and SNP array-based segmental aneuploidy profiling a highly complex chromosomal rearrangement involving at least three breaks in chromosome 1 and seven breaks in chromosome 7. Chromosome banding revealed an inversion of region 7q32.1–7q35 on the derivative chromosome 7. FISH with region-specific BACs mapped both inversion breakpoints and revealed additional breaks and structural changes in the CNTNAP2 gene. Two gene segments were transposed and inserted into the 1q31.2 region, while the CNTNAP2 segment bet... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2590481 Tue, 07 Jul 2009 15:27:44 +0100 2590481 A modifier locus on chromosome 5 contributes to L1 cell adhesion molecule X-linked hydrocephalus in mice http://www.medworm.com/index.php?rid=2568197&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F77424gq43747j524%2F Abstract  Humans with L1 cell adhesion molecule (L1CAM) mutations exhibit X-linked hydrocephalus, as well as other severe neurological disorders. L1-6D mutant mice, which are homozygous for a deletion that removes the sixth immunoglobulin-like domain of L1cam, seldom display hydrocephalus on the 129/Sv background. However, the same L1-6D mutation produces severe hydrocephalus on the C57BL/6J background. To begin to understand how L1cam deficiencies result in hydrocephalus and to identify modifier loci that contribute to X-linked hydrocephalus by genetically interacting with L1cam, we conducted a genome-wide scan on F2 L1-6D mice, bred from L1-6D 129S2/SvPasCrlf and C57BL/6J mice. Linkage studies, utilizing chi-square tests and quantitative trait loci mapping techniques, were pe... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2568197 Tue, 30 Jun 2009 15:41:09 +0100 2568197 COL25A1 triggers and promotes Alzheimer’s disease-like pathology in vivo http://www.medworm.com/index.php?rid=2500673&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F06pj01pk00767172%2F Abstract  Collagen XXV alpha 1 (COL25A1) is a collagenous type II transmembrane protein purified from senile plaques of Alzheimer’s disease (AD) brains. COL25A1 alleles have been associated with increased risk for AD in a Swedish population. COL25A1 is specifically expressed in neurons and binds to aggregated Aβ in vitro. However, its contribution to the pathogenesis of AD and in vivo function are unknown. Here, we report that over-expression of COL25A1 in transgenic mice increases p35/p25 and β-site APP-cleaving enzyme 1 (BACE1) levels, facilitates intracellular aggregation and extracellular matrix deposits of Aβ, and causes synaptophysin loss and astrocyte activation. COL25A1 mice displayed reduced anxiety-like behavior in elevated plus maze and open field tests and si... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2500673 Tue, 23 Jun 2009 06:03:59 +0100 2500673 Reduced levels of survival motor neuron protein leads to aberrant motoneuron growth in a Xenopus model of muscular atrophy http://www.medworm.com/index.php?rid=2500674&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc33887m0573608tu%2F Abstract  Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. The loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN) protein in human, leads to reduced levels of SMN and eventually to SMA. Here, we ask if the amphibian Xenopus tropicalis can be a good model system to study SMA. Inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. Of note, early developmental patterning of muscles and motor neurons is unaffected in this system as well as acetylcholine receptors clustering. Muscular atrophy seems to rather result from aberrant pathfinding and growth arrest and/or shortening of motor axons. This event occurs i... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2500674 Thu, 11 Jun 2009 14:05:14 +0100 2500674 A novel variation in the Twinkle linker region causing late-onset dementia http://www.medworm.com/index.php?rid=2500675&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc28qp6908554l571%2F We describe five patients from two unrelated Alsatian families with the new R374W variation in the Twinkle linker region who progressively developed an autosomal dominant multisystem disorder with PEO, hearing loss, myopathy, dysphagia, dysphonia, sensory neuropathy, and late-onset dementia resembling Alzheimer’s disease. These observations demonstrate that Twinkle variations in the linker domain alter cerebral function and further implicate disrupted mitochondrial DNA integrity in the pathogenesis of dementia. Content Type Journal ArticleCategory ORIGINAL ARTICLEDOI 10.1007/s10048-009-0202-4Authors Andoni Echaniz-Laguna, Hôpital Civil Département de Neurologie BP 426 67091 Strasbourg FranceJean-Baptiste Chanson, Hôpital Civil Département de Neurologie BP 426 67091 Strasbour... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2500675 Wed, 10 Jun 2009 10:04:06 +0100 2500675 U1 snRNA mis-binding: a new cause of CMT1B http://www.medworm.com/index.php?rid=2445629&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F42677120j3218m76%2F We report the molecular characterization of two splice mutations in two different French families affected with a late onset form of Charcot–Marie–Tooth disease type 1B (CMT1B), an autosomal dominant inherited disorder caused by mutations in the myelin protein zero gene. The first substitution, c.306G>A, located in exon 3, does not change the codon p.Val102Val but is co-transmitted with the disease in the first family. The second substitution, c.675+3dup, is an insertion of a T at position +3 of intron 5. To identify the functional impact of these nucleotide changes on splicing and because no RNA sample was available, we used in silico prediction and in vitro splicing assay. Mutation c.306G>A increases the strength of a preexisting cryptic donor site at position c.304 which... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2445629 Thu, 28 May 2009 09:19:35 +0100 2445629 SCA27 caused by a chromosome translocation: further delineation of the phenotype http://www.medworm.com/index.php?rid=2445630&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F42t3228556587121%2F We report of a spinocerebellar ataxia (SCA)27 in a daughter and her mother whose karyotype is 46, XX t(5;13)(q31.2;q33.1). The translocation breakpoint is identical in both patients, disrupting the gene-encoding fibroblast growth factor 14 isoform b (FGF14-1b). Clinically, both show signs of SCA, although the daughter is the most affected with early onset cerebellar ataxia, microcephaly, and severe mental retardation. FGF14-1b is the predominant isoform in brain, where it interacts with the voltage gated Na channel. Fgf14−/− mice develop ataxia and paroxysmal dyskinesia and have cognitive deficits. One missense and one non-sense mutation in FGF14 have previously been linked to SCA27. Truncation of one allele in our patients suggests that haploinsuffiency of FGF14 can cause SCA27. ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2445630 Wed, 27 May 2009 06:04:32 +0100 2445630 Alu-specific microhomology-mediated deletions in CDKL5 in females with early-onset seizure disorder http://www.medworm.com/index.php?rid=2445631&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu23375752456ww5k%2F Abstract  Mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene in Xp22.13 have been associated with infantile spasms, early-onset intractable epilepsy, and a Rett syndrome (RTT)-like phenotype. Using array comparative genomic hybridization, we identified variable-sized microdeletions involving exons 1–4 of the CDKL5 gene in three females with early-onset seizures. Two of these deletions were flanked by Alu repetitive elements and may have resulted from either non-allelic homologous recombination or the microhomology-mediated Fork Stalling and Template Switching/Microhomology-Mediated Break-Induced Replication mechanism. Our findings demonstrate the first instance of genomic deletion as the molecular basis of CDKL5 deficiency in females and highlight the importance o... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2445631 Wed, 27 May 2009 06:04:31 +0100 2445631 LRRK2 and GBA mutations differentially affect the initial presentation of Parkinson disease http://www.medworm.com/index.php?rid=2431438&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8u2720347712504j%2F Abstract   GBA and LRRK2 mutations increase susceptibility to Parkinson disease (PD), which is characterized by various disabling symptoms. An extended cohort of 600 Ashkenazi PD patients was screened for the LRRK2 G2019S and for eight GBA mutations. Reported initial symptoms were compared between three genotypic groups of patients: carriers of GBA mutations, carriers of LRRK2 G2019S mutation, and non-carriers. More LRRK2 G2019S carriers reported muscle stiffness (rigidity, p = 0.007) and balance disturbances (p = 0.008), while more GBA mutation carriers reported slowness (bradykinesia, p = 0.021). These results suggest distinct effects of LRRK2 or GBA mutations on the initial symptoms of PD. Content Type Journal ArticleCategory SHORT COMMUNICATIONDOI 10.1007/s10... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2431438 Thu, 21 May 2009 06:16:12 +0100 2431438 Mitochondrial ND3 as the novel causative gene for Leber hereditary optic neuropathy and dystonia http://www.medworm.com/index.php?rid=2431439&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp8543r4676150214%2F Abstract  Leber hereditary optic neuropathy and dystonia (LDYT) is a mitochondrial disorder associated with variable combinations of vision loss and progressive generalized dystonia. LDYT is a unique oxidative phosphorylation disorder caused by mutations in mitochondrial ND6 or ND4 gene. In this paper, we describe a Chinese family with 18 LDYT patients. The comprehensive nucleotide sequence analysis of the entire mitochondrial genome using resequencing microarray revealed a mutation (mtND3*10197A (m.10197G>A)) substituting a threonine for a highly conserved alanine at codon 47 of MTND3 on the background of haplogroup D4b. Quantitative analysis of the heteroplasmy of the mutation revealed a homoplasmy in the leukocytes of all the affected individuals on the maternal side.... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2431439 Thu, 21 May 2009 06:16:11 +0100 2431439 Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management http://www.medworm.com/index.php?rid=2421809&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F452m483282p2wx45%2F Abstract  While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecula... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2421809 Thu, 14 May 2009 07:07:33 +0100 2421809 Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3–q25.1 http://www.medworm.com/index.php?rid=2395717&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn632750k606x5641%2F Abstract  Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity in the lower limbs. They are clinically heterogeneous, and pure forms as well as complicated forms with other accompanying clinical findings are known. HSPs are also genetically heterogeneous. We performed clinical and genetic studies in a consanguineous family with five affected members. A genome scan using 405 microsatellite markers for eight members of the family identified candidate gene loci, and subsequent fine mapping in 16 members identified the gene locus responsible for the HSP. The clinical manifestations were very early onset spastic paraplegia (SPG) accompanied by mental retardation and ocular signs. The gene locus was identified as the interval 102.05–106.64 Mbp ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2395717 Tue, 05 May 2009 06:08:46 +0100 2395717 A novel 16p locus associated with BSCL2 hereditary motor neuronopathy: a genetic modifier? http://www.medworm.com/index.php?rid=2373490&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw63m46629v25jt28%2F We describe the neurological, electrophysiological, and genetic features of autosomal dominant distal hereditary motor neuronopathy (HMN) in a three-generation Dutch family, including 12 patients with distal muscle weakness and atrophy. The severity of disease ranged from disabling muscle weakness to a subclinical phenotype. Neurologic exams of nine patients and nerve conduction studies (NCS) and myography in five endorsed the variable presentations of HMN in this family, including patients with only lower (four), upper (one), or both upper and lower extremities involvement (four). Asymmetrical or strictly unilateral disease was noted in three patients. Three also showed pyramidal features. A genome-wide search combining SNP arrays (250K) with parametric linkage analysis identified a... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2373490 Sat, 25 Apr 2009 07:28:47 +0100 2373490 Movement disorder and neuronal migration disorder due to ARFGEF2 mutation http://www.medworm.com/index.php?rid=2363018&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7g2653vl4v7373w%2F We report a child with a severe choreadystonic movement disorder, bilateral periventricular nodular heterotopia (BPNH), and secondary microcephaly based on compound heterozygosity for two new ARFGEF2 mutations (c.2031_2038dup and c.3798_3802del), changing the limited knowledge about the phenotype. The brain MRI shows bilateral hyperintensity of the putamen, BPNH, and generalized atrophy. Loss of ARFGEF2 function affects vesicle trafficking, proliferation/apoptosis, and neurotransmitter receptor function. This can explain BPNH and microcephaly. We hypothesize that the movement disorder and the preferential damage to the basal ganglia, specifically to the putamen, may be caused by an increased sensitivity to degeneration, a dynamic dysfunction due to neurotransmitter receptor mislocaliz... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2363018 Wed, 22 Apr 2009 08:13:01 +0100 2363018 Recent origin and spread of a common Welsh MAPT splice mutation causing frontotemporal lobar degeneration http://www.medworm.com/index.php?rid=2338411&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F17p6314416x1w336%2F Abstract  IVS10+16C>T is the most prevalent mutation in the microtubule-associated protein tau gene (MAPT) causing frontotemporal lobar degeneration (FTLD) in populations of British descent. A highly conserved 17q21 haplotype was identified in IVS10+16C>T chromosomes from North Wales, Greater Manchester and the London areas of the UK, Australia, and the USA, suggesting the occurrence of a common founder effect. To test this hypothesis, the age of the mutation was estimated by parametric and Bayesian analysis of linkage disequilibrium's decay over generations, and the results were compared with historical and geographical data on FTLD families. The inferred age (23 generations; 95% confidence interval, 9–74 generations) dates the most recent common ancestor of IVS10+1... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2338411 Tue, 14 Apr 2009 06:02:05 +0100 2338411 A novel de novo MFN2 mutation causing CMT2A with upper motor neuron signs http://www.medworm.com/index.php?rid=3095599&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8uh7145g607q1153%2F Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-009-0188-yAuthors S. Ajroud-Driss, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 710 N. Lake Shore Drive, 14th floor Abbott Hall #1426 Chicago IL 60611 USAF. Fecto, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago IL 60611 USAK. Ajroud, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago IL 60611 USAY. Yang, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago I... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095599 Tue, 07 Apr 2009 05:48:31 +0100 3095599 A novel de novo MFN2 mutation causing CMT2A with upper motor neuron signs http://www.medworm.com/index.php?rid=2338412&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8uh7145g607q1153%2F Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-009-0188-yAuthors S. Ajroud-Driss, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 710 N. Lake Shore Drive, 14th floor Abbott Hall #1426 Chicago IL 60611 USAF. Fecto, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago IL 60611 USAK. Ajroud, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago IL 60611 USAY. Yang, Northwestern University Davee Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine 300E Superior St, Tarry 13-715 Chicago I... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2338412 Tue, 07 Apr 2009 05:48:31 +0100 2338412 Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease http://www.medworm.com/index.php?rid=3095600&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F868410x2535g1355%2F Abstract  We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population. Content Type Journal ArticleCategory Or... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095600 Thu, 26 Mar 2009 08:05:37 +0100 3095600 Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease http://www.medworm.com/index.php?rid=2321258&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F868410x2535g1355%2F Abstract  We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population. Content Type Journal ArticleCategory Or... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2321258 Thu, 26 Mar 2009 08:05:37 +0100 2321258 Lrrk2 R1441G-related Parkinson’s disease: evidence of a common founding event in the seventh century in Northern Spain http://www.medworm.com/index.php?rid=2294215&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F54n679x8463l5283%2F Abstract  Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene together represent the most common genetic determinant of Parkinson’s disease (PD) identified to date. The vast majority of patients with LRRK2-related PD reported in the literature carry one of three pathogenic substitutions: G2019S, R1441C, or R1441G. While G2019S and R1441C are geographically widespread, R1441G is most prevalent in the Basque Country and is rare outside of Northern Spain. We sought to better understand the processes that have shaped the current distribution of R1441G. We performed a haplotype analysis of 29 unrelated PD patients heterozygous for R1441G and 85 wild-type controls using 20 markers that spanned 15.1 Mb across the LRRK2 region. Nine of the patients were of Basque origi... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2294215 Tue, 24 Mar 2009 07:09:26 +0100 2294215 Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models http://www.medworm.com/index.php?rid=2281695&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3q832258p4366110%2F Abstract  Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous disorder. All mendelian patterns of inheritance have been described. We identified a homozygous p.A335V mutation in the MED25 gene in an extended Costa Rican family with autosomal recessively inherited Charcot-Marie-Tooth neuropathy linked to the CMT2B2 locus in chromosome 19q13.3. MED25, also known as ARC92 and ACID1, is a subunit of the human activator-recruited cofactor (ARC), a family of large transcriptional coactivator complexes related to the yeast Mediator. MED25 was identified by virtue of functional association with the activator domains of multiple cellular and viral transcriptional activators. Its exact physiological function in transcriptional regulation remains obscure. Th... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2281695 Tue, 17 Mar 2009 07:05:42 +0100 2281695 Ashkenazi Parkinson’s disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries http://www.medworm.com/index.php?rid=3095601&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp148q40516236608%2F Abstract  The LRRK2 G2019S mutation is a major genetic determinant of Parkinson’s disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived ∼1,830 (95% CI 1,560–2,160) years ago, around the second century, after the second Jewish Diaspora. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-009-0186-0Authors Anat Bar-Shira, Tel Aviv Sourasky ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095601 Fri, 13 Mar 2009 10:12:39 +0100 3095601 Ashkenazi Parkinson’s disease patients with the LRRK2 G2019S mutation share a common founder dating from the second to fifth centuries http://www.medworm.com/index.php?rid=2267982&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp148q40516236608%2F Abstract  The LRRK2 G2019S mutation is a major genetic determinant of Parkinson’s disease (PD) across the world that occurs at an elevated frequency in Ashkenazi Jews. We determined the LRRK2 haplotypes in 77 G2019S carriers, mostly Ashkenazi Jews, and in 50 noncarrier Ashkenazi PD patients, using 16 genetic markers. A single haplotype was detected in all mutation carriers, indicating that these individuals share a common founder. Using a maximum-likelihood method, we estimate that Ashkenazi Jews with G2019S share a common ancestor who lived ∼1,830 (95% CI 1,560–2,160) years ago, around the second century, after the second Jewish Diaspora. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-009-0186-0Authors Anat Bar-Shira, Tel Aviv Sourasky ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2267982 Fri, 13 Mar 2009 10:12:39 +0100 2267982 Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging http://www.medworm.com/index.php?rid=3095602&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp651j070u50tn2j7%2F We report our linkage data on a family with late-infantile NCL and show that the disease in this family is due to a homozygous novel mutation in the most recently described NCL gene (MFSD8). We use clinical data from our patients and the few others that have previously been reported to delineate the phenotype associated with mutations in this gene. We conclude that the phenotype is fairly consistent, which is a helpful guide to clinicians as they decide on the most cost-effective molecular testing strategies for NCLs. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-009-0185-1Authors M. A. Aldahmesh, King Faisal Specialist Hospital and Research Center Developmental Genetics Unit, Department of Genetics MBC 03 P.O. Box 3354 Riyadh 11211 Saudi ArabiaZ. N. Al-Ha... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095602 Wed, 11 Mar 2009 15:03:10 +0100 3095602 Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: a common theme emerging http://www.medworm.com/index.php?rid=2267983&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp651j070u50tn2j7%2F We report our linkage data on a family with late-infantile NCL and show that the disease in this family is due to a homozygous novel mutation in the most recently described NCL gene (MFSD8). We use clinical data from our patients and the few others that have previously been reported to delineate the phenotype associated with mutations in this gene. We conclude that the phenotype is fairly consistent, which is a helpful guide to clinicians as they decide on the most cost-effective molecular testing strategies for NCLs. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-009-0185-1Authors M. A. Aldahmesh, King Faisal Specialist Hospital and Research Center Developmental Genetics Unit, Department of Genetics MBC 03 P.O. Box 3354 Riyadh 11211 Saudi ArabiaZ. N. Al-Ha... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2267983 Wed, 11 Mar 2009 15:03:10 +0100 2267983 The impact of spermine synthase (SMS) mutations on brain morphology http://www.medworm.com/index.php?rid=3095603&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7745v38w163l430m%2F Abstract  Snyder–Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age- and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect re... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095603 Wed, 11 Mar 2009 15:03:08 +0100 3095603 The impact of spermine synthase ( SMS ) mutations on brain morphology http://www.medworm.com/index.php?rid=2267984&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7745v38w163l430m%2F Abstract  Snyder–Robinson syndrome (SRS) is a form of X-linked mental retardation resulting from mutations in spermine synthase (SMS), which impact neurodevelopment and cognitive outcome. We obtained cerebral, cerebellum, hippocampus, and red nucleus volumes from two males with SRS and 24 age- and gender-matched typically developing controls using volumetric neuroimaging analyses. Total brain volume was enlarged in males with SRS while cerebellum, hippocampus, and red nucleus volumes tended to be reduced compared to controls. Mutations of the X chromosome may modulate the risk for mental retardation through altered early neurodevelopment, disruption in receptor function, and ongoing neural organization and plasticity. Disruption of SMS function may negatively affect re... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2267984 Wed, 11 Mar 2009 15:03:08 +0100 2267984 Extended tracts of homozygosity identify novel candidate genes associated with late-onset Alzheimer’s disease http://www.medworm.com/index.php?rid=2255684&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk516030742367k56%2F Abstract  Large tracts of extended homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended homozygosity (greater than 1 Mb in length) in a population of 837 late-onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1, and ADRB3. We also compared the total numbers... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2255684 Sat, 07 Mar 2009 12:17:03 +0100 2255684 Molecular analysis of NPC1 and NPC2 gene in 34 Niemann–Pick C Italian Patients: identification and structural modeling of novel mutations http://www.medworm.com/index.php?rid=3095604&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj736080648010k25%2F Abstract  Niemann–Pick C, the autosomal recessive neuro-visceral disease resulting from a failure of cholesterol trafficking within the endosomal–lysosomal pathway, is due to mutations in NPC1 or NPC2 genes. We characterized 34 unrelated patients including 32 patients with mutations in NPC1 gene and two patients in NPC2 gene. Overall, 33 distinct genotypes were encountered. Among the 21 unpublished NPC1 alleles, 15 were due to point mutations resulting in 13 codon replacements (p.C100S, p.P237L, p.R389L, p.L472H, p.Y634C, p.S636F, p.V780G, p.Q921P, p.Y1019C, p.R1077Q, p.L1102F, p.A1187V, and p.L1191F) and in two premature stop codons (p.R934X and p.Q447X); a new mutant carried two in cis mutations, p.[L648H;M1142T] and four other NPC1 alleles were small deletions/insertion... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=3095604 Sat, 28 Feb 2009 15:29:31 +0100 3095604 Molecular analysis of NPC1 and NPC2 gene in 34 Niemann–Pick C Italian Patients: identification and structural modeling of novel mutations http://www.medworm.com/index.php?rid=2231512&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj736080648010k25%2F Abstract  Niemann–Pick C, the autosomal recessive neuro-visceral disease resulting from a failure of cholesterol trafficking within the endosomal–lysosomal pathway, is due to mutations in NPC1 or NPC2 genes. We characterized 34 unrelated patients including 32 patients with mutations in NPC1 gene and two patients in NPC2 gene. Overall, 33 distinct genotypes were encountered. Among the 21 unpublished NPC1 alleles, 15 were due to point mutations resulting in 13 codon replacements (p.C100S, p.P237L, p.R389L, p.L472H, p.Y634C, p.S636F, p.V780G, p.Q921P, p.Y1019C, p.R1077Q, p.L1102F, p.A1187V, and p.L1191F) and in two premature stop codons (p.R934X and p.Q447X); a new mutant carried two in cis mutations, p.[L648H;M1142T] and four other NPC1 alleles were small deletions/insertion... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2231512 Sat, 28 Feb 2009 15:29:31 +0100 2231512 Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes http://www.medworm.com/index.php?rid=2221577&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw128qg5721ml5454%2F Abstract  It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosa... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2221577 Wed, 25 Feb 2009 10:35:04 +0100 2221577 Reply to the “Letter to the Editors” by Steven Buyske http://www.medworm.com/index.php?rid=2215649&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpg2646621121h571%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-009-0180-6Authors K. Abu-Elneel, University of California Santa Barbara Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology Santa Barbara CA 93106 USAT. Liu, University of California Santa Barbara Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology Santa Barbara CA 93106 USAF. S. Gazzaniga, University of California Santa Barbara Neuroscience Research Institute, Department of Molecular Cellular and Developmental Biology Santa Barbara CA 93106 USAY. Nishimura, University of California at Los Angeles Department of Neurology, David Geffen School of Medicine Los Angeles CA 90095-1769 USAD. P. Wall, Harvard Medical School The Center for ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2215649 Tue, 24 Feb 2009 09:49:13 +0100 2215649 Robust quantification of the SMN gene copy number by real-time TaqMan PCR http://www.medworm.com/index.php?rid=2215650&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe8350575qj206466%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10048-009-0181-5Authors Ilsa Gómez-Curet, Alfred I. duPont Hospital for Children Nemours Biomedical Research P.O. Box 269 Wilmington DE 19899 USAKaryn G. Robinson, Alfred I. duPont Hospital for Children Nemours Biomedical Research P.O. Box 269 Wilmington DE 19899 USAVicky L. Funanage, Alfred I. duPont Hospital for Children Nemours Biomedical Research P.O. Box 269 Wilmington DE 19899 USAThomas O. Crawford, Johns Hopkins University Departments of Neurology and Pediatrics Baltimore MD USAMena Scavina, Alfred I. duPont Hospital for Children Nemours Biomedical Research P.O. Box 269 Wilmington DE 19899 USAWenlan Wang, Alfred I. duPont Hospital for Children Nemours Biomedical Research P.O. Box 269 Wilmington DE 19899 USA Journal... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2215650 Tue, 24 Feb 2009 09:49:10 +0100 2215650 Comment on the article “Heterogeneous dysregulation of microRNAs across the autism spectrum” by Abu-Elneel et al. http://www.medworm.com/index.php?rid=2215651&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm176p332v8572684%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-009-0179-zAuthors Steven Buyske, Rutgers University Department of Statistics & Biostatistics Hill Center, 110 Frelinghuysen Road Piscataway NJ 08854 USA Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2215651 Tue, 24 Feb 2009 09:49:09 +0100 2215651 The spectrum of somatic and germline NF1 mutations in NF1 patients with spinal neurofibromas http://www.medworm.com/index.php?rid=2199502&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb8535204t7037v42%2F Abstract  Neurofibromatosis type 1 (NF1) is a common inherited complex multi-system disorder associated with the growth of various benign and malignant tumors. About 40% of NF1 patients develop spinal tumors, of whom some have familial spinal neurofibromatosis (FSNF), a variant form of NF1 in which patients present with multiple bilateral spinal tumors but have few other clinical features of the disease. We have studied 22 spinal neurofibromas derived from 14 unrelated NF1 patients. Seven of these patients satisfied the diagnostic criteria of NF1 while the remaining seven had only few features of NF1. The latter group defined as FSNF harbored significantly higher number of missense or missense and splice-site germline mutations compared to the group with classical NF1. This... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2199502 Tue, 17 Feb 2009 10:05:24 +0100 2199502 Association between migraine and a functional polymorphism at the dopamine β-hydroxylase locus http://www.medworm.com/index.php?rid=2190344&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd5p68l7j45437u61%2F Abstract  Migraine is a common neurological disorder with a significant genetic component. Although a number of linkage and association studies have been undertaken, the number and identity of all migraine susceptibility genes has yet to be defined. The existence of dopaminergic hypersensitivity in migraine has been recognised on a pharmacological basis and some studies have reported genetic association between migraine and dopamine-related gene variants. Our laboratory has previously reported association of migraine with a promoter STR marker in the dopamine beta hydroxylase (DBH) gene. In the present study, we analysed two additional DBH markers in two independent migraine case–control cohorts. These two markers are putative functional SNPs, one within the promoter (−... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2190344 Sat, 14 Feb 2009 10:20:33 +0100 2190344 A new complex homozygous large rearrangement of the PINK1 gene in a Sudanese family with early onset Parkinson’s disease http://www.medworm.com/index.php?rid=2186886&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmj4j808202524632%2F Abstract   PARK2 and PINK1 gene mutations are involved in recessive early onset Parkinson’s disease (EOPD). In order to determine the causative mutations in three affected sibs from a consanguineous Sudanese family with EOPD, multiplex ligation-dependent probe amplification was performed and revealed that the patients were homozygous for a deletion of PINK1 exons 4 to 8. Breakpoint analysis revealed a complex rearrangement combining a large deletion and the insertion of a sequence duplicated from the DDOST gene intron 2, located near the PINK1 gene. As breakpoint sequences displayed only three base pairs of homology, this rearrangement may result from Fork Stalling and Template Switching mechanism. This third large rearrangement of PINK1 enlarges the mutation spectrum and,... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2186886 Fri, 13 Feb 2009 08:10:32 +0100 2186886 Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1 http://www.medworm.com/index.php?rid=2152515&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1h6620665g662u4p%2F Abstract  Mast syndrome (SPG21) is an autosomal-recessive complicated form of hereditary spastic paraplegia characterized by dementia, thin corpus callosum, white matter abnormalities, and cerebellar and extrapyramidal signs in addition to spastic paraparesis. A nucleotide insertion resulting in premature truncation of the SPG21 gene product acidic cluster protein 33 (ACP33)/maspardin underlies this disorder, likely causing loss of protein function. However, little is known about the function of maspardin. Here, we report that maspardin localizes prominently to cytoplasm as well as to membranes, possibly at trans-Golgi network/late endosomal compartments. Immunoprecipitation of maspardin with identification of coprecipitating proteins by mass spectrometry revealed the aldehy... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2152515 Sat, 31 Jan 2009 07:25:19 +0100 2152515 Examination of association of genes in the serotonin system to autism http://www.medworm.com/index.php?rid=2147164&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl85047027626877x%2F Abstract  Autism is characterized as one of the pervasive developmental disorders, a spectrum of often severe behavioral and cognitive disturbances of early development. The high heritability of autism has driven multiple efforts to identify genetic variation that increases autism susceptibility. Numerous studies have suggested that variation in peripheral and central metabolism of serotonin (5-hydroxytryptamine) may play a role in the pathophysiology of autism. We screened 403 autism families for 45 single nucleotide polymorphisms in ten serotonin pathway candidate genes. Although genome-wide linkage scans in autism have provided support for linkage to various loci located within the serotonin pathway, our study does not provide strong evidence for linkage to any specific ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2147164 Thu, 29 Jan 2009 07:41:57 +0100 2147164 A LRRK2 G2019S mutation carrier from Turkey shares the Japanese haplotype http://www.medworm.com/index.php?rid=2140854&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe21584473603k25h%2F This study revealed a Turkish patient heterozygous for the G2019S mutation sharing the Japanese haplotype. To the best of our knowledge, it is the first time that the G2019S-associated Japanese haplotype has been reported in a different population. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-009-0173-5Authors C. Pirkevi, Boğaziçi University Molecular Biology and Genetics Department, Neurodegeneration Research Laboratory 34342 Istanbul TurkeyS. Lesage, INSERM, UMR S679 75013 Paris FranceC. Condroyer, INSERM, UMR S679 75013 Paris FranceH. Tomiyama, Juntendo University School of Medicine Department of Neurology Tokyo JapanN. Hattori, Juntendo University School of Medicine Department of Neurology Tokyo JapanS. Ertan, University of Istanbul Department of ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2140854 Tue, 27 Jan 2009 07:59:02 +0100 2140854 Whole-genome conditional two-locus analysis identifies novel candidate genes for late-onset Parkinson’s disease http://www.medworm.com/index.php?rid=2128330&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7273873mg57331q%2F We present the first whole-genome conditional two-locus analysis in Parkinson’s disease (PD). We scanned the entire genome and selected markers that interacted with a set of well-known loci previously associated to PD (SNCA, Parkin, LRRK2, UCHL1, DJ-1, PINK and MAPT). Our work describes several loci potentially related to PD risk which interact with SNCA, PARK1 and LRRK2 markers. We propose conditional whole-genome two-locus association analysis as a valuable method that might be helpful in re-analysing and re-interpreting data from whole-genome association studies. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-009-0170-8Authors A. González-Pérez, NeoCodex Department of Structural Genomics Avda. Charles Darwin 6 41092 Seville SpainJ. Gayán, NeoCodex... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2128330 Wed, 21 Jan 2009 23:23:26 +0100 2128330 Familial hemiplegic migraine: linkage to chromosome 14q32 in a Spanish kindred http://www.medworm.com/index.php?rid=2120615&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw1168r251406w260%2F Abstract  We sought to map the disease-causing gene in a large Spanish kindred with familial hemiplegic migraine (FHM). Patients were classified according to the ICHD-II criteria. After ruling out linkage to known migraine genetic loci, a single nucleotide polymorphism-based, 0.62-cM density genome-wide scan was performed. Among 13 affected subjects, FHM was the prevailing migraine phenotype in six, migraine with aura in four and migraine without aura in three. Linkage analysis revealed a disease locus in a 4.15-Mb region on 14q32 with a maximum two-point logarithm of odds (LOD) score of 3.1 and a multipoint parametric LOD score of 3.8. This genomic region does not overlap with the reported migraine loci on 14q21–22. Sequence analysis of three candidate genes in the regio... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2120615 Tue, 20 Jan 2009 09:48:27 +0100 2120615 A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated http://www.medworm.com/index.php?rid=2094498&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj7234808q63v4473%2F Abstract  Hereditary sensory neuropathy type 1 (HSAN I) is an autosomal dominant inherited neurodegenerative disorder of the peripheral nervous system associated with mutations in the SPTLC1 subunit of the serine palmitoyltransferase (SPT). Four missense mutations (C133W, C133Y, V144D and G387A) in SPTLC1 were reported to cause HSAN I. SPT catalyses the condensation of Serine and Palmitoyl-CoA, which is the first and rate-limiting step in the de novo synthesis of ceramides. Earlier studies showed that C133W and C133Y mutants have a reduced activity, whereas the impact of the V144D and G387A mutations on the human enzyme was not tested yet. In this paper, we show that none of the HSAN I mutations interferes with SPT complex formation. We demonstrate that also V144D has a redu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2094498 Fri, 09 Jan 2009 11:05:24 +0100 2094498