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. Sun, 21 Mar 2010 16:44:29 +0100 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 http://www.medworm.com/index.php?rid=2051798&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb8051743250750g1%2F We report the clinical course of a 7-year-old girl with CIPA and proven NTRK1 mutation. In addition to recurrent dislocation of the left hip joint and avascular necrosis of the left talus, the patient also presented with recurrent infections secondary to hypogammaglobulinemia, a feature not previously known to be associated with CIPA. The patient was treated with regular administration of intravenous immunoglobulins. Conservative treatment of the recurrent left hip dislocation by cast immobilization and bracing was implemented to stabilize the joint. The implication of the immune system of the reported patient broadens the clinical phenotype associated with NTRK1 mutations. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-008-0165-xAuthors Sara Sebnem Ki... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2051798 Wed, 17 Dec 2008 08:04:05 +0100 2051798 http://www.medworm.com/index.php?rid=2051797&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu43438421540643h%2F Abstract  Mutations in GDAP1, an outer mitochondrial membrane protein responsible for recessive Charcot-Marie-Tooth disease (CMT4A), have also been associated with CMT2K, a dominant form of the disease. The three CMT2K patients we studied carried a novel dominant GDAP1 mutation, C240Y (c.719G > A). Mitochondrial respiratory chain complex I activity in fibroblasts from CMT2K patients was 40% lower than in controls, whereas the tubular mitochondria were 33% larger in diameter and the mitochondrial mass was 20% greater. Thus, besides the regulatory role GDAP1 plays in mitochondrial network dynamics, it may also be involved in energy production and in the control of mitochondrial volume. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-008-016... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2051797 Wed, 17 Dec 2008 08:04:05 +0100 2051797 http://www.medworm.com/index.php?rid=2051799&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft7262m2847618214%2F Abstract  Population-level familial risks are not available for amyotrophic lateral sclerosis (ALS), and a few studies have analyzed familial association of ALS with other diseases. We used the Swedish Multigeneration Register to identify family members and link them to the Hospital Discharge Register to calculate standardized incidence ratios (SIRs) for familial association in ALS and 33 autoimmune diseases. Among 4,970 ALS patients, familial SIR for offspring of affected parents was 4.71, for singleton siblings, it was 29.83, and for members of multiplex families, it was 1,100; 1.1% of the offspring had an affected parent, and 2.2% an affected sibling. The high risks among siblings without affected parents may suggest recessive inheritance. The SIR for spouse correlation ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2051799 Wed, 17 Dec 2008 08:04:04 +0100 2051799 http://www.medworm.com/index.php?rid=2032572&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg882366475uk6430%2F The objective of this study was to examine RNA expression in blood of subjects with Duchenne muscular dystrophy (DMD). Whole blood was collected into PAX gene tubes and RNA was isolated for 3- to 20-year-old males with DMD (n = 34) and for age- and gender-matched normal healthy controls (n = 21). DMD was confirmed by genetic testing in all subjects. RNA expression was measured on Affymetrix whole-genome human U133 Plus 2.0 GeneChips. Using a Benjamini–Hochberg false discovery rate of 0.05 to correct for multiple comparisons, an unpaired t test for DMD versus controls yielded 10,763 regulated probes with no fold change cutoff, 1,467 probes with >|1.5|-fold change, 191 probes with >|2.0|-fold change, and 59 probes with a >|2.5|-fold change. These genes (probes) separat... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=2032572 Wed, 10 Dec 2008 07:56:25 +0100 2032572 http://www.medworm.com/index.php?rid=1995781&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6397120441135503%2F We report a mutation frequency of 2.3% in REEP1 in ADHSP, suggesting REEP1 mutation is a relatively uncommon cause of ADHSP in a population of patients drawn from the UK. The phenotype of ADHSP associated with REEP1 mutation is broader than initially reported. The spastic paraparesis in SPG31 may be complicated by the presence of amyotrophy, bulbar palsy and/or peripheral neuropathy. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0163-zAuthors Channa Hewamadduma, University of Sheffield The Academic Neurology Unit, Section of Neuroscience, Medical School Sheffield UKChristopher McDermott, University of Sheffield The Academic Neurology Unit, Section of Neuroscience, Medical School Sheffield UKJanine Kirby, University of Sheffield The Academic Neurology Uni... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1995781 Wed, 26 Nov 2008 20:00:40 +0100 1995781 http://www.medworm.com/index.php?rid=1995780&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnlj40487546n2lt7%2F We report the identification of the first de novo mutation at a highly conserved residue within the polyalanine stretch in the N-terminal region of the brain-dominant protein isoform MeCP2_e1 in a girl with classical Rett syndrome. The missense mutation, p.Ala2Val, leads to severe developmental delay, microcephaly, no language, severe epilepsy, and cognitive impairment. To evaluate the pathogenic potentials of the MECP2 mutation specific to the MeCP2_e1 isoform detected in this patient, full-length wild-type and mutated cDNAs were cloned in eukaryotic expression vectors to generate a fusion protein with c-myc, and constructs were transfected in COS7 cells. In vitro studies demonstrated that, like wild-type MeCP2e_1, the N-terminal mutant is localized in the nucleus. Neither transcript... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1995780 Wed, 26 Nov 2008 20:00:40 +0100 1995780 http://www.medworm.com/index.php?rid=1989507&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff784519160548318%2F Abstract  Autosomal recessive spastic ataxia of Charlevoix–Saguenay is a neurodegenerative disorder characterized by early-onset, spastic ataxia and peripheral neuropathy, with or without mental retardation. The array of mutations in SACS has expanded worldwide after the first description in Quebec. We herein report the identification of an unconventional SACS mutation, a large-scale deletion sized ∼1.5 Mb encompassing the whole gene, in two unrelated patients. The clinical phenotype of the patients was similar to more canonical ARSACS cases, though it is was complicated by the unusual presence of hearing loss. Our findings suggest that a “microdeletion” on chromosome 13q12 represents a novel allelic variant associated with ARSACS, stressing the need for an expan... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1989507 Tue, 25 Nov 2008 06:48:52 +0100 1989507 http://www.medworm.com/index.php?rid=1979567&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm485847w75945812%2F Abstract  Mutations in LRRK2 gene are the most frequent cause of Parkinson’s disease (PD) described, but their prevalence varies between populations. Patients, 418, with PD and 138 unrelated controls from the Basque Country were screened for LRRK2 G2019S and R1441G mutations. Of the patients, 3.82% were heterozygous carriers of G2019S and 13.15% of R1441G. G2019S frequency was higher in non-Basque population (6.0%), while R1441G was more common in Basque origin population (22.4%). Our conclusion is that both G2019S and R1441G mutations’ frequency varies markedly between Basque and non-Basque origin population reinforcing the importance of ethnicity consideration when establishing mutation prevalence. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1979567 Thu, 20 Nov 2008 08:11:32 +0100 1979567 http://www.medworm.com/index.php?rid=1911062&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh83453j2326q07k7%2F Content Type Journal ArticleCategory Invited EditorialDOI 10.1007/s10048-008-0152-2Authors G. C. Ebers, University of Oxford The Wellcome Trust Centre for Human Genetics, Department of Clinical Neurology Roosevelt Drive Oxford OX3 7BN UK Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1911062 Fri, 24 Oct 2008 06:50:26 +0100 1911062 http://www.medworm.com/index.php?rid=1911063&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F151894681160v313%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10048-008-0160-2Authors Sascha Vermeer, Radboud University Nijmegen Medical Centre Department of Human Genetics Internal postal code 849 P.O. Box 9100 6500 HB Nijmegen The NetherlandsRowdy P. P. Meijer, Radboud University Nijmegen Medical Centre Department of Human Genetics Internal postal code 849 P.O. Box 9100 6500 HB Nijmegen The NetherlandsBenjamin J. Pijl, Radboud University Nijmegen Medical Centre Department of Ophthalmology Nijmegen The NetherlandsJanneke Timmermans, Radboud University Nijmegen Medical Centre Department of Cardiology Nijmegen The NetherlandsJohannes R. M. Cruysberg, Radboud University Nijmegen Medical Centre Department of Ophthalmology Nijmegen The NetherlandsMaaike M. Bos, Radboud University Nijmegen Medi... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1911063 Fri, 24 Oct 2008 06:50:25 +0100 1911063 http://www.medworm.com/index.php?rid=1883079&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft0u3843708170701%2F In conclusion, the PGRN Gly35fs mutation causes frontotemporal dementia with variable clinical presentation in a large Swedish family, most likely through nonsense-mediated decay of mutant PGRN mRNA and resulting haploinsufficiency. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0155-zAuthors Lena Skoglund, Uppsala University Department of Public Health and Caring Sciences Dag Hammarskjölds väg 20 751 85 Uppsala SwedenRoseMarie Brundin, Uppsala University Department of Public Health and Caring Sciences Dag Hammarskjölds väg 20 751 85 Uppsala SwedenTommie Olofsson, Uppsala University Department of Surgical Sciences Uppsala SwedenHannu Kalimo, Uppsala University Department of Genetics and Pathology Uppsala SwedenSofie Ingvast, Uppsala University Departm... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1883079 Wed, 15 Oct 2008 10:50:53 +0100 1883079 http://www.medworm.com/index.php?rid=1883078&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbjv480q645783836%2F Abstract  We performed a prospective analysis on 14 11q- patients to determine the relationship between the degree of cognitive impairment and relative deletion size. Seventeen measures of cognitive function were assessed. All nine patients with a deletion of at least 12.1 Mb had severe global cognitive impairment, with full-scale IQ <50, whereas all five patients with smaller deletions, ≤11.8 Mb, demonstrated mild cognitive impairment, with a full-scale IQ of 63 or higher (p < 0.001). Among these five patients, the two patients with the larger deletions (11.4, 11.8 Mb) had a selective impairment in freedom from distractability compared to the three patients with smaller deletions (≤9.1 Mb). We propose the presence of a proximal critical reg... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1883078 Wed, 15 Oct 2008 10:50:53 +0100 1883078 http://www.medworm.com/index.php?rid=1883077&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk1820622024u773j%2F Abstract  Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotyp... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1883077 Wed, 15 Oct 2008 10:50:53 +0100 1883077 http://www.medworm.com/index.php?rid=1875573&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl1667w4388307335%2F We describe a novel mutation in the previously identified MFSD8 gene in a family with a common phenotype of LINCL, but no clinical report of vision loss. Our results enlarge the mutational and perhaps the nosological spectrum of one of the recently identified subtypes of NCL, called CLN7. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0153-1Authors E. Stogmann, General Hospital, Medical University of Vienna Department of Neurology Waehringer Guertel 18-20 1090 Vienna AustriaS. El Tawil, Ain Shams University Department of Neurology Cairo EgyptJ. Wagenstaller, GSF National Research Centre for Environment and Health Institute of Human Genetics Neuherberg GermanyA. Gaber, Ain Shams University Department of Neurology Cairo EgyptS. Edris, Ain Shams University D... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1875573 Sat, 11 Oct 2008 11:17:15 +0100 1875573 http://www.medworm.com/index.php?rid=1875574&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F47p642p95231w775%2F Abstract  The hallmark of neurofibromatosis type 1 (NF1) are multiple dermal neurofibromas. They show high inter- and intrafamilial variability for which the influence of modifying genes is discussed. NF1 patients presenting microdeletions spanning NF1 and several contiguous genes have an earlier onset and higher number of dermal neurofibromas than classical NF1 patients, pointing to one of the deleted genes as modifier. Expression analysis of 13 genes of the microdeletion region in dermal neurofibromas and other tissues revealed four candidates for the modification of neurofibroma formation: CENTA2, RAB11FIP4, C17orf79, and UTP6. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-008-0154-0Authors B. Bartelt-Kirbach, University of Ulm Institute of... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1875574 Sat, 11 Oct 2008 11:17:14 +0100 1875574 http://www.medworm.com/index.php?rid=1867930&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxqw3783g5g3133x5%2F Abstract  In the era of complex disease genetics, the consideration of familial risks is important in the assessment of the likely success of these studies. In the present article, we study familial risks for multiple sclerosis (MS) among parents and offspring, singleton siblings, twins, and spouses when a family member was diagnosed with MS or any of 33 other autoimmune diseases. The availability of a Multigeneration Register in Sweden provides a reliable access to families throughout the last century. The diseases in individual family members were obtained through linkage to the Hospital Discharge Register. With a total patient population of 425,102 of whom 11,154 were diagnosed with MS, this is the largest population-based family study on these diseases to date. Standard... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1867930 Thu, 09 Oct 2008 09:09:35 +0100 1867930 http://www.medworm.com/index.php?rid=1850414&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F91lllg324r8n6p55%2F In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case–control and family-based findings suggests that these loci currently represent... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1850414 Thu, 02 Oct 2008 09:27:37 +0100 1850414 http://www.medworm.com/index.php?rid=1828836&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1k13j7627l286129%2F This study design makes it possible to replicate reported LOAD risk alleles while contributing novel information about the mechanism by which they might affect that risk. Alleles in ACE, APOE, BDNF, DAPK1, and TF are significantly associated with CSF Aβ levels. In vitro analysis of the TF SNP showed a change in secreted Aβ consistent with the CSF phenotype and known Alzheimer’s disease variants, demonstrating the utility of this approach in identifying SNPs that influence risk for disease via an Aβ-related mechanism. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0150-4Authors John S. K. Kauwe, B8134 Washington University School of Medicine Department of Psychiatry 660 S. Euclid Ave. St. Louis MO USAJun Wang, B8134 Washington University School of M... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1828836 Wed, 24 Sep 2008 08:20:57 +0100 1828836 http://www.medworm.com/index.php?rid=1824084&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb591177r7757j60x%2F We report on a splice acceptor site mutation in intron 9 of ALS2 (IVS9–2A>T) in a German patient from nonconsanguineous parents. The mutation results in skipping of exon 10. This causes a frame-shift in exon 11 and a premature stop codon. Analysis of the parental ALS2 gene revealed heterozygosity for the mutation in the mother but not in the father. Therefore, we studied polymorphic markers scattered along chromosome 2 in both parents and the patient and found maternal uniparental disomy in the patient. While homozygosity was observed at several loci of chromosome 2 including ALS2, other loci were heterozygous, i.e., both maternal alleles were present. The findings can be explained by at least four recombination events during maternal meiosis followed by a meiosis I error and post... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1824084 Tue, 23 Sep 2008 10:15:17 +0100 1824084 http://www.medworm.com/index.php?rid=1824083&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu8u8373l31687128%2F Abstract  Recent findings demonstrated the role of neurotransmitters in the aetiopathogenesis of sudden unexpected deaths in infancy. Although genes involved in serotonin metabolism have been proposed as risk factors for sudden infant death syndrome (SIDS), the contribution of additional neurotransmitters and genes different from the serotonin transporter (SLC6A4, 5-HTT) has not been investigated. Considering the common metabolic pathway and synergism between dopamine and serotonin, the role of dopamine transporter (SLC6A3, DAT) and monoamine oxidase A (MAOA) genes in SIDS and stillbirth (sudden intrauterine unexplained death, SIUD) was investigated. Genotypes and allelic frequencies of DAT and MAOA were determined in 20 SIDS and five stillbirth cases and compared with 150 co... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1824083 Tue, 23 Sep 2008 10:15:17 +0100 1824083 http://www.medworm.com/index.php?rid=1811063&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fwghm01227872p263%2F Content Type Journal ArticleCategory Acknowledgement to RefereesDOI 10.1007/s10048-008-0146-0 Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1811063 Thu, 18 Sep 2008 06:37:03 +0100 1811063 http://www.medworm.com/index.php?rid=1793894&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp3m2557470813480%2F Abstract  The recent discovery of genomic reprogramming of human somatic cells into induced pluripotent stem cells offers an innovative and relevant approach to the study of human genetic and neurogenetic diseases. By reprogramming somatic cells from patient samples, cell lines can be isolated that self-renew indefinitely and have the potential to develop into multiple different tissue lineages. Additionally, the rapid progress of research on human embryonic stem cells has led to the development of sophisticated in vitro differentiation protocols that closely mimic mammalian development. In particular, there have been significant advances in differentiating human pluripotent stem cells into defined neuronal types. Here, we summarize the experimental approaches employed in t... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1793894 Sat, 13 Sep 2008 08:10:43 +0100 1793894 http://www.medworm.com/index.php?rid=1790000&cid=s_33318_50_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm5664ww45x1367g3%2F Abstract  Mutations in the spatacsin gene have recently been identified as the genetic cause of autosomal–recessive spastic paraplegia (SPG) with thin corpus callosum, mapping to chromosome 15p13–21. While several nonsense and frameshift mutations as well as splice mutations have been identified, large genomic deletions have not yet been found, potentially due to the absence of an efficient analysis tool. After complete sequencing of 12 autosomal recessive hereditary spastic paraplegia patients with suggestive clinical signs, we were able to define nine SPG11 cases but were left with three patients in which only one SPG11 mutation could be identified by direct sequencing. In these patients, we performed high-resolution comparative genomic hybridization using a predesigne... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1790000 Fri, 12 Sep 2008 08:07:37 +0100 1790000 http://www.medworm.com/index.php?rid=1749755&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1774127222224141%2F We report the molecular characterization of 12 unrelated Italian patients affected with Sandhoff disease (SD), a recessively inherited disorder caused by mutations in HEXB gene. We identified 11 different mutations of which six are novel: one large deletion of 2,406 nt, (c.299+1471_408del2406), one frameshift mutation c.965delT (p.I322fsX32), one nonsense c.1372C>T (p.Q458X), and three splicing mutations (c.299G>T, c.300-2A>G and c.512-1G>T). One allele was only characterized at the messenger RNA (mRNA) level (r = 1170_1242del). Real-time polymerase chain reaction analysis of the HEXB mRNA from fibroblasts derived from patients carrying the novel point mutations showed that the presence of the premature termination codon in the transcript bearing the mutation c.9... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1749755 Sat, 30 Aug 2008 16:22:42 +0100 1749755 http://www.medworm.com/index.php?rid=1749754&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh864205622020282%2F We describe the clinical, radiographic, and genetic features of a large consanguineous Moroccan family in which bilateral occipital polymicrogyria segregated as an autosomal recessive trait. Six affected members of the family had partial complex seizures often associated with behavioral abnormalities. On MRI, three patients had a thickened irregular cortex in the lateral occipital lobes with small gyri. Ahigh-density genome-wide scan with 10,000 SNPs established linkage by homozygosity mapping to a 14-Mb region on chromosome 6q16–q22. Candidate genes by function (TUBE1, GRIK2, GPRC6A, GPR6, NR2E1, MICAL1, and MARCKS) in this locus were screened for mutations. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0143-3Authors Bouchra Ouled Amar Ben Cheikh, ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1749754 Sat, 30 Aug 2008 16:22:42 +0100 1749754 http://www.medworm.com/index.php?rid=1729208&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp840468ulv622502%2F Abstract  The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson’s disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29–3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1729208 Thu, 21 Aug 2008 09:32:41 +0100 1729208 http://www.medworm.com/index.php?rid=1713589&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv2351743n00wt781%2F The objective of this study is to determine the frequency of mutations in these PARK genes in a Korean early-onset Parkinson disease (EOPD) cohort. The authors sequenced 35 exons in SNCA, PARKIN, DJ-1, PINK1, and LRRK2 in 72 unrelated EOPD (age-at-onset ≤50) recruited from ten movement disorders clinics in South Korea. Gene dosage change of the aforementioned genes was studied using multiple ligation-dependent probe amplification. We found four patients with PARKIN mutations, which were homozygous deletion of exon 4, compound heterozygous deletion of exon 2 and exon 4, heterozygous deletion of exon 4, and heterozygous nonsense mutation (Q40X). Four patients had PINK1 mutations; a compound heterozygous mutation (N367S and K520RfsX522) and three heterozygous mutations (G32R, R279H, and... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1713589 Fri, 15 Aug 2008 06:19:53 +0100 1713589 http://www.medworm.com/index.php?rid=1693507&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fgv7535137u122211%2F In this study, we describe the localization of a novel form of autosomal recessive, primary focal torsion dystonia using a genomewide search in a large consanguineous Lebanese family with three affected individuals. Homozygosity mapping with 382 microsatellite markers was conducted. Linkage analysis and haplotype construction allowed us to identify a novel locus designated as DYT17, within a 20.5-Mb interval on chromosome 20. Of the 270 known genes spread on this interval, 27 candidate genes were tested and excluded as responsible for the disease. Fine mapping by identification of other dystonia families linked to chromosome 20 and sequencing of candidate genes in the refined interval is required in order to identify the causative gene in DYT17. Content Type Journal ArticleCategor... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1693507 Fri, 08 Aug 2008 06:53:53 +0100 1693507 http://www.medworm.com/index.php?rid=1691513&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx47651364r12231h%2F Abstract  Lissencephaly spectrum (LIS) is one of the most severe neuronal migration disorders that ranges from agyria/pachygyria to subcortical band heterotopia. Approximately 80% of patients with the LIS spectrum carry mutations in either the LIS1 or DCX (doublecortin) genes which have an opposite gradient of severity. The aim of the study was to evaluate in detail the phenotype of DCX-associated lissencephaly and to look for genotype–phenotype correlations. Of the 180 male patients with DCX-related lissencephaly, 33 males (24 familial cases and nine cases with de novo mutations) were found with hemizygous DCX mutations and were clinically and genetically assessed here. DCX mutation analysis revealed that the majority of mutations were missense (79.2%), clustered in the two e... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1691513 Thu, 07 Aug 2008 10:00:00 +0100 1691513 http://www.medworm.com/index.php?rid=1668063&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr149224261462477%2F We describe a male patient with a phenotype highly suggestive of AOA2, but only one point mutation found by sequencing of the SETX gene. Further analysis revealed a large out-of-frame tandem duplication, encompassing exons 7, 8, 9 and 10. This duplication event occurred obviously by unequal homologous recombination between AluY sequences. Gross SETX deletions or duplications might be an underestimated cause of AOA2. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-008-0139-zAuthors Larissa Arning, Ruhr University Department of Human Genetics 44780 Bochum GermanyLudger Schöls, Eberhard Karls University Tübingen Department of Neurology, Hertie-Institute for Clinical Brain Research Tuebingen GermanyHuriye Cin, Ruhr University Department of Human Genetics 447... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1668063 Tue, 29 Jul 2008 06:51:49 +0100 1668063 http://www.medworm.com/index.php?rid=1668062&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2j2n5p8lx6887635%2F Abstract  Nitric oxide synthase (NOS) genes (NOS1, NOS2A, and NOS3) may create excess nitric oxide that contributes to neurodegeneration in Parkinson’s disease (PD). NOS genes might also interact with one another or with environmental factors in PD. Coding and tagging single nucleotide polymorphisms (SNPs) (27 NOS1, 18 NOS2A, and five NOS3 SNPs) were genotyped in families with PD (1,065 cases and 1,180 relative and other controls) and were tested for allelic associations with PD using the association in the presence of linkage test and the pedigree disequilibrium test (PDT), allelic associations with age-at-onset (AAO) using the quantitative transmission disequilibrium test, and interactions using the multifactor dimensionality reduction—PDT. Gene–environment interactio... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1668062 Tue, 29 Jul 2008 06:51:49 +0100 1668062 http://www.medworm.com/index.php?rid=1593303&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa30451146t326740%2F In this report, we describe a deletion in the 5′ region of the Kcnn2 gene encoding the SK2 subunit in the mouse neurological frissonnant (fri) mutant. The frissonnant mutant phenotype is characterized by constant rapid tremor and locomotor instability. It has been suggested, based merely on its phenotype, as a potential model for human Parkinson disease. We used a positional cloning strategy to identify the mutation underlying the frissonnant phenotype. We narrowed the genetic disease interval and identified a 3,441-bp deletion in the Kcnn2 gene, one of the three candidate genes present in the interval. Expression studies showed complete absence of normal Kcnn2 transcripts while some tissue-specific abnormal truncated variants were detected. Intracellular electrophysiological recording... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1593303 Sat, 05 Jul 2008 06:23:13 +0100 1593303 http://www.medworm.com/index.php?rid=1537724&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1180228534129349%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-008-0134-4Authors José A. Peña, Universidad del País Vasco Departamento de Genética y Antropología Física, Facultad de Ciencia y Tecnología 48080 Bilbao SpainMiguel A. Alfonso-Sánchez, Universidad del País Vasco Servicio de Investigación Genómica, Banco de ADN, Facultad de Farmacia 01006 Vitoria SpainAna B. Rodríguez-Martínez, Universidad del País Vasco Departamento de Zoología y Biología Celular Animal, Facultad de Farmacia 01006 Vitoria SpainMarian M. de Pancorbo, Universidad del País Vasco Servicio de Investigación Genómica, Banco de ADN, Facultad de Farmacia 01006 Vitoria Spain Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1537724 Sat, 21 Jun 2008 06:58:36 +0100 1537724 http://www.medworm.com/index.php?rid=1537725&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqw3p307v414l5836%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-008-0135-3Authors H.-S. Lee, National Institutes of Health National Institute of Neurological, Disorders and Stroke Bethesda MD 20892-9404 USAL. G. Goldfarb, National Institutes of Health National Institute of Neurological, Disorders and Stroke Bethesda MD 20892-9404 USA Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1537725 Sat, 21 Jun 2008 06:58:35 +0100 1537725 http://www.medworm.com/index.php?rid=1534957&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F502364384m142272%2F Abstract  Limb-girdle muscular dystrophy type 2A (LGMD2A) is an autosomal recessive disorder caused by mutations in the CAPN3 gene. Its definitive diagnosis is laborious, since the clinical phenotype is often similar to other types of muscular dystrophy and since the CAPN3 gene encompasses a large genomic region with more than 300 pathogenic mutations described to date. In fact, it is estimated that nearly 25% of the cases with a phenotype suggestive of LGMD2A do not have mutations in the CAPN3 gene and that, in up to 22% of the cases, only one mutation is identified. In the present work, we have characterised CAPN3 messenger RNA (mRNA) expression in peripheral blood, and we have performed a retrospective diagnostic study with 26 LGMD2A patients, sequencing a transcript of CAP... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1534957 Thu, 19 Jun 2008 07:02:33 +0100 1534957 http://www.medworm.com/index.php?rid=1534958&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl785u152131t304g%2F This study finds that altered miRNA expression levels are observed in postmortem cerebellar cortex from autism patients, a finding which suggests that dysregulation of miRNAs may contribute to autism spectrum phenotype. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0133-5Authors Kawther Abu-Elneel, University of California Santa Barbara Neuroscience Research Institute, and Department of Molecular Cellular and Developmental Biology Santa Barbara CA 93106 USATsunglin Liu, University of California Santa Barbara Neuroscience Research Institute, and Department of Molecular Cellular and Developmental Biology Santa Barbara CA 93106 USAFrancesca S. Gazzaniga, University of California Santa Barbara Neuroscience Research Institute, and Department of Molecular Cell... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1534958 Thu, 19 Jun 2008 07:02:32 +0100 1534958 http://www.medworm.com/index.php?rid=1448649&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg302421426uh4510%2F Abstract  X-linked adrenoleukodystrophy and hemophilia A are two distinct, potentially devastating, genetic diseases whose corresponding genes are located in close proximity on the X chromosome. Here we report a family with members affected with both conditions, only the second such family ever reported. Although a structural genomic rearrangement involving both genes was initially predicted to underlie this extremely rare phenotype, genotyping revealed the unlikely occurrence of two individual point mutations. Given the impact of this result on the heritability of the two disorders within the family, this case illustrates the significance of performing detailed molecular analysis in patients with multiple genetic disorders. Content Type Journal ArticleCategory Original A... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1448649 Thu, 15 May 2008 06:37:59 +0100 1448649 http://www.medworm.com/index.php?rid=1434320&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5w4163552354u053%2F Abstract  Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: MIM 270550) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. This disorder, considered to be rare, was first described in the late seventies among French Canadians in the isolated Charlevoix-Saguenay region of Quebec. Nowadays, it is known that the disorder is not only limited to this region but occurs worldwide. Our objective was to identify cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in Dutch patients with recessive early-onset cerebellar ataxia by sequencing the complete SACS gene. In a Dutch cohort of 43 index patients with ataxia onset before age 25, we identified 16 index patients (total 23 ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1434320 Fri, 09 May 2008 06:24:45 +0100 1434320 http://www.medworm.com/index.php?rid=1431624&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu21555t5r71588k8%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-008-0130-8Authors Lúcia Inês Macedo-Souza, University of São Paulo Institute of Biosciences Center for Studies of the Human Genome São Paulo São Paulo BrazilFernando Kok, University of São Paulo Institute of Biosciences Center for Studies of the Human Genome São Paulo São Paulo BrazilSilvana Santos, University of São Paulo Institute of Biosciences Center for Studies of the Human Genome São Paulo São Paulo BrazilLuciana Licinio, University of São Paulo Institute of Biosciences Center for Studies of the Human Genome São Paulo São Paulo BrazilKarina Lezirovitz, University of São Paulo Institute of Biosciences Center for Studies of the Human Genome São Paulo São Paulo BrazilRafaella M. P. Nascimen... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1431624 Thu, 08 May 2008 06:08:54 +0100 1431624 http://www.medworm.com/index.php?rid=1431625&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk4238gxh83017674%2F This study also includes the re-analysis of one of the original US pedigrees reporting the CMTX3 locus. The large Australian family shared the complete disease haplotype with our original NZ/UK family, while the American family shared only the distal portion of the disease haplotype. Comparison of the frequency of the CMTX3 haplotype to the normal population showed strong statistical evidence (p < 0.0001) indicating that the smaller shared haplotype is identical by descent. This suggests that the new CMTX3 family, our previously reported family, and the original American CMTX3 family have a common ancestor, and the disease in these families is caused by a founder mutation. The ancestral recombination observed in the American family refines the CMTX3 interval to a 2.5 Mb region... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1431625 Tue, 06 May 2008 19:02:32 +0100 1431625 http://www.medworm.com/index.php?rid=1377664&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu7706450w4025207%2F Abstract  A nonsense mutation (R419X) in the human cereblon gene [mutation (mut) CRBN] causes a mild type of autosomal recessive nonsyndromal mental retardation (ARNSMR). CRBN, a cytosolic protein, regulates the assembly and neuronal surface expression of large-conductance Ca2+-activated K+ channels (BKCa) in brain regions involved in memory and learning. Using the real-time quantitative polymerase chain reaction, we show that mut CRBN disturbs the development of adult brain BKCa isoforms. These changes are predicted to result in BKCa channels with a higher intracellular Ca2+ sensitivity, faster activation, and slower deactivation kinetics. Such alterations may contribute to cognitive impairments in patients with mild ARNSMR. Content Type Journal ArticleCategory Short Commu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1377664 Tue, 15 Apr 2008 07:54:01 +0100 1377664 http://www.medworm.com/index.php?rid=1362220&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1u79q364j3l00720%2F In conclusion, this study supports a lower frequency of PGRN mutations amongst FTLD patients in Italy compared to literature data and further underlies the genetic heterogeneity of FTLD. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0127-3Authors Barbara Borroni, University of Brescia Department of Neurology Brescia ItalySilvana Archetti, University of Brescia Laboratory of Biotechnology, Department of Diagnostic of Laboratories Brescia ItalyAntonella Alberici, University of Brescia Department of Neurology Brescia ItalyChiara Agosti, University of Brescia Department of Neurology Brescia ItalyMassimo Gennarelli, Genetic Unit, IRCCS Brescia Brescia ItalyBarbara Bigni, University of Brescia Department of Neurology Brescia ItalyCristian Bonvicini, Genetic Uni... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1362220 Tue, 08 Apr 2008 07:26:07 +0100 1362220 http://www.medworm.com/index.php?rid=1331184&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg65211l7p8640580%2F Content Type Journal ArticleCategory Letter to the editorAuthors D. N. Louis, Molecular Neuro-Oncology Laboratory, CNY6, Massachusetts General Hospital and Harvard Medical School, 149 Thirteenth Street, Boston, MA 02129, USA e-mail louis@helix.mgh.harvard.edu Tel.: +1-617-7265510 Fax: +1-617-7265079 USY. Ino, Molecular Neuro-Oncology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA USD. C. R. Wahrer, Center for Cancer Risk Analysis, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA USD. W. Bell, Center for Cancer Risk Analysis, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA USD. A. Haber, Center for Cancer Risk Analysis, Massachusetts General Hospital and Harvard ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1331184 Tue, 25 Mar 2008 18:46:26 +0100 1331184 http://www.medworm.com/index.php?rid=1331183&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq787713547m71138%2F ABSTRACT   The lysosomal storage of lipofuscins is the common pathological feature that characterizes the infantile, late-infantile, juvenile (Batten's disease), and Finnish-variant neuronal ceroid lipofuscinosis (INCL, LINCL, JNCL and FNCL), which are due to mutations in the genes CLN1 , CLN2 , CLN3 , and CLN5 , respectively. The CLN1 and CLN2 genes encode lysosomal enzymes, but the CLN3 and CLN5 genes encode membrane-spanning proteins. Why deficiencies of lysosomal enzymes and membrane-spanning proteins produce similar clinical phenotypes and pathological changes is still unanswered. We hypothesize that CLN -encoded proteins may comprise a functional pathogenic pathway, in which protein associations may play important roles. To test this hypoth... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1331183 Tue, 25 Mar 2008 18:46:26 +0100 1331183 http://www.medworm.com/index.php?rid=1331185&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8377l372127m5612%2F ABSTRACT¶We have sequenced all mitochondrial complex I and tRNA genes in five pairs of monozygotic twins with a longitudinal diagnosis of idiopathic Parkinson disease (PD). At the time of molecular genetic analysis, four of the pairs were discordant for PD. Five novel homoplasmic sequence variants, including two missense mutations (ND2 4924 G/A, ND3 10192 C/T), were detected in mitochondrial genes of complex I in four of the pairs. In addition, a total of 20 known polymorphisms affecting both complex I and tRNA genes was found. Importantly, mitochondrial DNA sequences were identical in diseased and non-affected siblings of each pair. Our results demonstrate that missense mutations of mitochondrial complex I may occur in clinically discordant parkinsonian twins, questioning the dire... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1331185 Tue, 25 Mar 2008 18:46:25 +0100 1331185 http://www.medworm.com/index.php?rid=1317456&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6253q84371382125%2F This study indicates DHPLC as an important tool in the detection of low-level mosaicism, as does it illustrate the importance of considering somatic and germline mosaicism in the case of apparent de novo mutation. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0125-5Authors Ofir T. Betsalel, VU University Medical Center Department of Clinical Chemistry, (Metabolic Unit PK1x009) De Boelelaan 1117 1081 HV Amsterdam The NetherlandsJiddeke M. van de Kamp, VU University Medical Center Department of Clinical Genetics Amsterdam The NetherlandsCristina Martínez-Muñoz, VU University Medical Center Department of Clinical Chemistry, (Metabolic Unit PK1x009) De Boelelaan 1117 1081 HV Amsterdam The NetherlandsEfraim H. Rosenberg, VU University Medical Center Depart... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1317456 Wed, 19 Mar 2008 12:04:00 +0100 1317456 http://www.medworm.com/index.php?rid=1313863&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm0m56pkp7l10285j%2F Abstract  This work presents a detailed investigation of the genomic region surrounding the PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI) from several European countries, notably Spain. The main focus of the study was to explore the origins of the chromosomes carrying the D178N mutation by designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene. Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327, rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over Spain. To augment the geographical scope of our study, 13 further FFI cases from Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction with the analysis of genealogical data for a group of FFI pati... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1313863 Tue, 18 Mar 2008 08:14:24 +0100 1313863 http://www.medworm.com/index.php?rid=1307544&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl674kq184r81t180%2F We examined this region with 23 microsatellite markers using 124 North European (NE) families and 209 Caribbean Hispanic families with late-onset AD (FAD). Significant evidence for linkage was present in a 5-cM interval near 20 cM in both the NE FAD (LOD = 3.5) and the Caribbean Hispanic FAD (LOD = 2.2) datasets. We further investigated these families and an independent NE case–control dataset using 14 single nucleotide polymorphisms (SNPs). The initial screening of the region at ∼20 cM in the NE case–control dataset revealed significant association between AD and seven SNPs in several genes, with the strongest result for rs2532500 in TAPBPL (p = 0.006). For rs3741916 in GAPDH, the C allele, rather than the G allele as was observed by Li et al. (Proc Natl A... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1307544 Fri, 14 Mar 2008 07:28:52 +0100 1307544 http://www.medworm.com/index.php?rid=1300084&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv28t637x52232125%2F In conclusion, isoform-expression profiles in LB diseases represent additional evidence for the direct involvement of isoform-expression deregulation in the development of neurodegenerative disorders. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0124-6Authors Katrin Beyer, Autonomous University of Barcelona Department of Pathology, Hospital Germans Trias i Pujol 08916 Badalona Barcelona SpainMontserrat Domingo-Sàbat, Autonomous University of Barcelona Department of Pathology, Hospital Germans Trias i Pujol 08916 Badalona Barcelona SpainJordi Humbert, Autonomous University of Barcelona Department of Pathology, Hospital Germans Trias i Pujol 08916 Badalona Barcelona SpainCristina Carrato, Autonomous University of Barcelona Department of Pathology, Hospi... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1300084 Wed, 12 Mar 2008 07:17:11 +0100 1300084 http://www.medworm.com/index.php?rid=1287235&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F08r8g3118024u861%2F Abstract  Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three fa... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1287235 Thu, 06 Mar 2008 16:43:14 +0100 1287235 http://www.medworm.com/index.php?rid=1287236&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy2m0x38128524126%2F This study demonstrates the scarcity of this disease in France with estimated disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-008-0123-7Authors M. Y. Frédéric, INSERM, U827 Montpellier F-34000 FranceF. Clot, INSERM, UMR_S679 Neurologie & Thérapeutique Expérimentale Paris F-75013 FranceL. Cif, CHU Montpellier, Hôpital Guy de Chauliac, Service de Neurochirurgie Montpellier F-34000 FranceA. Blanchard, INSERM, U827 Montpellier F-34000 FranceA. Dürr, INSERM, UMR_S679 Neurologie & Thérapeutique Expérimentale Paris F-75013 FranceI. Vuillaume, CHRU de Lille, UF de Neurobiologie, Centre de Biologie-Pathologie Lille F-59037 FranceG. Lesca, Hôpital Edouard Herriot, service de Génétiqu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1287236 Thu, 06 Mar 2008 16:43:13 +0100 1287236 http://www.medworm.com/index.php?rid=1259645&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq552k75583726u68%2F We report here the first genome-wide analysis of CNVs in IS patients. In summary, our study did not detect any common genomic structural variation unequivocally linked to IS, although we cannot exclude that smaller CNVs or CNVs in genomic regions poorly covered by this methodology may confer risk for IS. The application of genome-wide SNP arrays now facilitates the evaluation of structural changes through the entire genome as part of a genome-wide genetic association study. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-008-0119-3Authors Mar Matarin, National Institute on Aging, National Institutes of Health Molecular Genetics Section Bethesda MD 20892 USAJavier Simon-Sanchez, National Institute on Aging, National Institutes of Health Molecular Genetics Se... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1259645 Thu, 21 Feb 2008 20:04:05 +0100 1259645 http://www.medworm.com/index.php?rid=1249981&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F58p701033230h387%2F Content Type Journal ArticleCategory Letter to the editorAuthors U. von Eitzen, Department of Neurology, Aachen University Medical School, Aachen, Germany DES. Kösel, Department of Neuromorphology, Max-Planck-Institute of Neurobiology, Martinsried, Germany DEE. M. Grasbon-Frodl, Molecular Neuropathology Laboratory, Institute of Neuropathology, Ludwig-Maximilians-University, Munich, Germany DER. Egensperger, Molecular Neuropathology Laboratory, Institute of Neuropathology, Hannover Medical School, Hannover, Germany DEM. B. Graeber, Department of Neuropathology, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, London, UK GB Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 Journal Volume Volume 3 Journal Issue Volume 3... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1249981 Wed, 20 Feb 2008 21:49:02 +0100 1249981 http://www.medworm.com/index.php?rid=1249980&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv1835r6v0163n834%2F ABSTRACT¶Tau is a microtubule-associated protein that binds to microtubules and promotes microtubule assembly. Six tau isoforms are produced in adult human brain by alternative mRNA splicing from a single gene. Inclusion of a 31-amino acid repeat encoded by exon 10 of the tau gene gives rise to the three isoforms with four microtubule-binding repeats each. The other three tau isoforms have three repeats each. Abundant neurofibrillary lesions made of tau protein constitute a defining neuropathological characteristic of Alzheimer's disease. Filamentous tau protein deposits are also the defining characteristic of other neurodegenerative diseases, many of which are frontotemporal dementias or movement disorders, such as Pick's disease, progressive supranuclear palsy and corticobasal deg... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1249980 Wed, 20 Feb 2008 21:48:56 +0100 1249980 http://www.medworm.com/index.php?rid=1249979&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl884747h125497h0%2F ABSTRACT¶We tested the hypothesis that Bis1, a gene involved in seizure regulation in mice which has been localized to the distal part of chromosome 4, was the same as the gene Kcnab2, encoding the β2-subunit for voltage-dependent K+ channels. Two facts suggested this hypothesis: Kcnab2 is located in the 3.1-cM confidence interval containing Bis1 and many studies have shown an involvement of K+ channels in the genesis of seizures. DNA sequence analysis of the coding sequence for Kcnab2 from JE/Le mice revealed no structural alterations which might affect Kcnab2 function. However, several nucleotide changes were observed.   Content Type Journal ArticleCategory Short communicationAuthors P. Zerr, Vollum Institute, Oregon Health Science University, 3181 SW Sam Jackson Park Roa... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1249979 Wed, 20 Feb 2008 21:48:52 +0100 1249979 http://www.medworm.com/index.php?rid=1195748&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg3227h07x2645515%2F Abstract  Benign adult familial myoclonic epilepsy (BAFME or FAME) is an autosomal dominant condition, characterized by shivering-like tremors of cortical origin, myoclonus, and epilepsy. Linkage to chromosomes 2p11.1-q12.2 and 8q23.1-q24.11 has been reported in Japanese and Italian families, respectively. We aimed to determine whether a common founder haplotype was shared by five BAFME families from southern Italy and attempted preliminary genotype–phenotype correlation analyses. Five Italian BAFME families were identified. One family has not been previously reported. DNA from 53 affected individuals was genotyped with highly polymorphic microsatellite markers spanning chromosomes 2p11.1-q12.2 and 8q23.1-q24.11. Multipoint linkage analysis was performed using LINKMAP 5.1... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1195748 Wed, 30 Jan 2008 16:29:31 +0100 1195748 http://www.medworm.com/index.php?rid=1158032&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa575426g1056w583%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-007-0117-xAuthors Tatsuaki Kurosaki, The University of Tokyo Department of Biological Sciences, Graduate School of Science Tokyo JapanTohru Matsuura, Nagoya University Graduate School of Medicine Division of Neurogenetics and Bioinfomatics, Center for Neurological Diseases and Cancer Nagoya 466-8550 JapanKinji Ohno, Nagoya University Graduate School of Medicine Division of Neurogenetics and Bioinfomatics, Center for Neurological Diseases and Cancer Nagoya 466-8550 JapanShintaroh Ueda, The University of Tokyo Department of Biological Sciences, Graduate School of Science Tokyo Japan Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1158032 Wed, 16 Jan 2008 15:49:50 +0100 1158032 http://www.medworm.com/index.php?rid=1155535&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk60065877t8tq706%2F Abstract  We have previously established a first whole genome transcriptomic profile of sporadic Parkinson’s disease (PD). After extensive brain tissue-based validation combined with cycles of iterative data analysis and by focusing on the most comparable cases of the cohort, we have refined our analysis and established a list of 892 highly dysregulated priority genes that are considered to form the core of the diseased Parkinsonian metabolic network. The substantia nigra pathways, now under scrutiny, contain more than 100 genes whose association with PD is known from the literature. Of those, more than 40 genes belong to the highly significantly dysregulated group identified in our dataset. Apart from the complete list of 892 priority genes, we present pathways revealing... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1155535 Tue, 15 Jan 2008 16:11:31 +0100 1155535 http://www.medworm.com/index.php?rid=1155534&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fuk13534161042223%2F We report here on the molecular characterization of a novel NF1 multiexonic deletion. The application of a multidisciplinary approach including multiplex ligation-dependent probe amplification, allelic segregation analysis, and fluorescent in situ hybridization allowed us to map the breakpoints in IVS27b and IVS48. Furthermore, the breakpoint junction was characterized by sequencing. Using bioinformatic analysis, we identified some recombinogenic motifs in close proximity to the centromeric and telomeric breakpoints and predicted the presence of a mutated messenger ribonucleic acid, which was deleted between exons 28 and 48 and encodes a neurofibromin that lacks some domains essential for its function. Through reverse transcriptase–polymerase chain reaction, the expression of the mu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1155534 Tue, 15 Jan 2008 16:11:31 +0100 1155534 http://www.medworm.com/index.php?rid=1152043&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0x66521231628566%2F This study provides evidence for a further RLS locus, thus supporting the picture of RLS as a genetically heterogenous complex trait. Content Type Journal ArticleCategory Original ArticleDOI 10.1007/s10048-007-0113-1Authors David Kemlink, GSF-National Research Center for Environment and Health Institute of Human Genetics Ingolstädter Landstrasse 1 85764 Neuherberg–Munich GermanyGiuseppe Plazzi, University of Bologna Department of Neurological Sciences Bologna ItalyRoberto Vetrugno, University of Bologna Department of Neurological Sciences Bologna ItalyFederica Provini, University of Bologna Department of Neurological Sciences Bologna ItalyOlli Polo, University of Turku Sleep Research Unit Turku FinlandKarin Stiasny-Kolster, Philipps University Marburg Department of Neurology Marbu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1152043 Mon, 14 Jan 2008 03:46:31 +0100 1152043 http://www.medworm.com/index.php?rid=1113814&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0072674257755364%2F Abstract  The protein leucine-rich repeat kinase 2 (LRRK2) is a key player in the pathogenesis of Parkinson’s disease (PD). Mutations in the LRRK2 gene account for up to 10% of all autosomal dominant forms of familiar and for approximately 1–3% of sporadic PD patients. Although the LRRK2 protein has many functional domains like a leucine-rich repeat domain, a Roc-GTPase domain, a kinase domain of the tyrosine kinase-like subfamily and multiple protein interaction domains (armadillo, ankyrin, WD40), the exact biological role of LRRK2 in the human brain is elusive. To gain more insight into the biological function of this protein, we monitored the changes in the expression profiles of SH-SY5Y cells, a dopaminergic neuroblastoma cell line, induced by a depletion of LRRK2 l... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1113814 Fri, 21 Dec 2007 16:08:54 +0100 1113814 http://www.medworm.com/index.php?rid=1105895&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn3l1414773472379%2F Abstract  Angiogenin (ANG) gene, coding for an angiogenic factor up-regulated by hypoxia and expressed in ventral horn motor neurons, is a novel candidate for the pathogenesis of amyotrophic lateral sclerosis (ALS). ALS is a fatal neurodegenerative disease characterized by the selective loss of cortical and spinal motor neurons. Missense mutations in ANG gene have been identified in two ALS populations from Northern Europe and North America, both in familial (FALS) and sporadic (SALS) patients, but they do not seem to be frequent in the Italian population. We performed a mutational screening in a large cohort of 737 Italian ALS patients, including 605 SALS and 132 FALS cases. We identified seven different mutations, five of which are novel, in nine patients (six SALS and thr... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1105895 Tue, 18 Dec 2007 15:48:54 +0100 1105895 http://www.medworm.com/index.php?rid=1092807&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg31883676j05p853%2F Abstract  Neonatal encephalopathy with seizures (NEWS) is a previously undescribed autosomal recessive disease of standard poodle puppies. Affected puppies are small and weak at birth. Many die in their first week of life. Those surviving past 1 week develop ataxia, a whole-body tremor, and, by 4 to 6 weeks of age, severe generalized clonic–tonic seizures. None have survived to 7 weeks of age. Cerebella from affected puppies were reduced in size and often contained dysplastic foci consisting of clusters of intermixed granule and Purkinje neurons. We used deoxyribonucleic acid samples from related standard poodles to map the NEWS locus to a 2.87-Mb segment of CFA36, which contains the canine ortholog of ATF2. This gene encodes activating transcription factor ... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1092807 Wed, 12 Dec 2007 15:42:43 +0100 1092807 http://www.medworm.com/index.php?rid=1074551&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy68g14446t754168%2F Abstract  Myotonic dystrophy type 2 (DM2) is caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the ZNF9 gene on chromosome 3q21. All studied DM2 mutations have been reported in Caucasians and share an identical haplotype, suggesting a common founder. We identified a Japanese patient with DM2 and showed that the affected haplotype is distinct from the previously identified DM2 haplotype shared among Caucasians. These data strongly suggest that DM2 expansion mutations originate from separate founders in Europe and Japan and are more widely distributed than previously recognized. Content Type Journal ArticleCategory Short CommunicationDOI 10.1007/s10048-007-0110-4Authors Tsukasa Saito, National Dohoku Hospital Department of Neurology Asahikawa JapanYoshinob... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1074551 Wed, 05 Dec 2007 16:36:52 +0100 1074551 http://www.medworm.com/index.php?rid=1074553&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx0g07515251423t5%2F Content Type Journal ArticleCategory ErratumDOI 10.1007/s10048-007-0108-yAuthors Ramesh C. Juyal, National Institute of Immunology, Aruna Asaf Ali Marg New Delhi 110067 IndiaMitashree Das, National Institute of Immunology, Aruna Asaf Ali Marg New Delhi 110067 IndiaSohan Punia, University of Delhi South Campus Department of Genetics New Delhi IndiaMadhuri Behari, All India Institute of Medical Sciences Department of Neurology New Delhi IndiaGeetika Nainwal, National Institute of Immunology, Aruna Asaf Ali Marg New Delhi 110067 IndiaSumit Singh, All India Institute of Medical Sciences Department of Neurology New Delhi IndiaPazhayannur V. Swaminath, National Institute of Mental Health and Neurosciences Department of Neurology Bangalore IndiaShyla T. Govindappa, National Institute of Menta... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1074553 Mon, 03 Dec 2007 18:17:27 +0100 1074553 http://www.medworm.com/index.php?rid=1074552&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fntm2n354883852x8%2F Abstract  Cerebral cavernous malformations (CCMs) are vascular abnormalities of the brain that can result in hemorrhagic stroke and seizures. Familial forms of CCM are inherited in an autosomal-dominant fashion, and three CCM genes have been identified. We recently determined that large genomic deletions in the CCM2 gene represent 22% of mutations in a large CCM cohort from the USA. In particular, a 77.6 kb deletion spanning CCM2 exons 2–10 displays an identical recombination event in eight CCM probands/families and appears to be common in the US population. In the current study, we report the identification of six additional probands/families from the USA with this same large deletion. Haplotype analysis strongly suggests that this common deletion derives from an anc... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1074552 Mon, 03 Dec 2007 18:17:26 +0100 1074552 http://www.medworm.com/index.php?rid=1019286&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv436565348472716%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-007-0107-zAuthors Cécile Saint-Martin, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceDelphine Bouteiller, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceGiovanni Stevanin, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceCyprian Popescu, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceCéline Charon, Centre National du Génotypage Evry FranceMerle Ruberg, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceStéphanie Baulac, GH Pitié-Salpêtrière INSERM, UMR 679 47 boulevard de l’hôpital 75013 Paris FranceEric LeGu... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=1019286 Fri, 09 Nov 2007 15:43:03 +0100 1019286 http://www.medworm.com/index.php?rid=994564&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F05t44126228m286t%2F Content Type Journal ArticleCategory Letter to the EditorsDOI 10.1007/s10048-007-0104-2Authors Noritoshi Arai, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyo Tokyo 113-8655 JapanAtsushi Kishino, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyo Tokyo 113-8655 JapanYuji Takahashi, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyo Tokyo 113-8655 JapanDaiji Morita, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyo Tokyo 113-8655 JapanKoichiro Nakamura, The University of Tokyo Department of Neurology, Graduate School of Medicine 7-3-1 Hongo Bunkyo Tokyo 113-8655 JapanTakahiro Yokoyama, Toranomon Bun-In Hos... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=994564 Tue, 30 Oct 2007 14:43:39 +0100 994564 http://www.medworm.com/index.php?rid=978810&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9231012062736v38%2F Content Type Journal ArticleCategory Acknowledgement to RefereesDOI 10.1007/s10048-007-0105-1 Journal neurogeneticsOnline ISSN 1364-6753Print ISSN 1364-6745 Journal Volume Volume 8 Journal Issue Volume 8, Number 4 / November, 2007 (Source: Neurogenetics) Neurogenetics journals http://www.medworm.com/rss/comments.php?id=978810 Tue, 23 Oct 2007 14:41:22 +0100 978810 http://www.medworm.com/index.php?rid=978809&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1755264412210202%2F Abstract  Alternative splicing is an important mechanism to generate a large number of mRNAs, thus increasing proteome diversity and tissue specificity. Three transcript variants of alpha-synuclein, a neuronal protein mainly involved in synapses, have been described so far. Whereas alpha-synuclein 140 is the whole and main transcript, alpha-synuclein 112 and 126 are short proteins that result from in-frame deletions of exons 3 and 5, respectively. Because the aforesaid alpha-synuclein isoforms show differential expression changes in Lewy body diseases (LBDs), in the present work, we searched for a fourth alpha-synuclein isoform and studied its expression levels in LBD brains. By using isoform-specific primers, isoform co-amplification and direct sequencing, we identified al... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=978809 Tue, 23 Oct 2007 14:41:22 +0100 978809 http://www.medworm.com/index.php?rid=964071&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0473337l148138x1%2F Abstract  The aim of the study was to identify chromosomal regions that may harbor putative genetic variants influencing age at onset in familial late-onset Alzheimer’s disease (LOAD). Data from a genome-wide scan that included genotyping of APOE were analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age at onset of 73.3 years multiply affected by LOAD. Two-point and multipoint analyses were conducted using variance component methods using 376 microsatellite markers with an average intermarker distance of 9.3 cM. Family-based test of association was also conducted for the same set of markers. Age at onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=964071 Wed, 17 Oct 2007 16:51:45 +0100 964071 http://www.medworm.com/index.php?rid=930348&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr616661351w955p7%2F Abstract  Muscle–eye–brain disease (MEB, OMIM 253280) is an autosomal recessive disorder characterized by a distinct triad of congenital muscular dystrophy, structural eye abnormalities, and cobblestone lissencephaly. Clinically, MEB patients present with early onset muscular hypotonia, severely compromised motor development, and mental retardation. Magnetic resonance imaging reveals a lissencephaly type II with hypoplasia of the brainstem and cerebellum. MEB is associated with mutations in the gene for protein O-mannose beta-1,2-N-acetylglucosaminyltransferase (POMGnT1, OMIM 606822). In this paper, we report the clinical findings of nine MEB patients from eight families. Eight of the nine patients presented typical features of MEB. However, a broad phenotypic variabilit... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=930348 Sat, 29 Sep 2007 17:28:56 +0100 930348 http://www.medworm.com/index.php?rid=848202&cid=s_33318_176_f&fid=33318&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F98388lj2m8qu3454%2F Abstract  The past year has seen a number of significant advances in our understanding of the neuropathological and molecular genetic basis of frontotemporal lobar degeneration (FTLD). Whereas, in the past, most attention focused on FTLD associated with tau-based pathology and microtubule associated protein tau gene (MAPT) mutations, there has recently been greater attention paid to non-tau FTLD. FTLD with tau-negative, ubiquitinated inclusions (FTLD-U) is now recognized as the most common pathology associated with clinical FTLD. Mutations in the progranulin gene (PGRN) have been identified as the cause of FTLD-U linked to chromosome 17. A rapidly growing number of PGRN mutations have been identified, and to date, all appear to cause FTLD by reducing the amount of functional P... Neurogenetics journals http://www.medworm.com/rss/comments.php?id=848202 Thu, 06 Sep 2007 07:04:17 +0100 848202