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 'European Journal of Medical Genetics' source. Thu, 09 Feb 2012 09:43:33 +0100 http://www.medworm.com/index.php?rid=5650898&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22285510%26dopt%3DAbstract Contradictory results in "Yq microdeletions in infertile men from Northern India" by Mittal et al. (Ann. Genet. 47 (2004) 331-337). Eur J Med Genet. 2012 Jan 8; Authors: Saliminejad K, Khorram Khorshid HR PMID: 22285510 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5650898 Sun, 08 Jan 2012 05:00:00 +0100 5650898 http://www.medworm.com/index.php?rid=5636038&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22274139%26dopt%3DAbstract We report a 19 year-old patient carrying a terminal 20p microdeletion. She displayed clinical features resembling those of two other previously described patients. We suggest that a specific phenotype can be associated with this chromosomal anomaly. Mental retardation, epilepsy, and dysmorphic signs including low-set ears and overfolded helices seem highly characteristic of this syndrome and may define major diagnostic criteria of a recognizable phenotype. Delayed closure of fontanella, delayed permanent teeth eruption, visual disturbances, prominent ear lobes, prominent nasal root and ridge, thin upper lip and brachydactyly may represent inconstant minor criteria. PMID: 22274139 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5636038 Thu, 05 Jan 2012 05:00:00 +0100 5636038 http://www.medworm.com/index.php?rid=5636040&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22266072%26dopt%3DAbstract Authors: Olson HE, Shen Y, Poduri A, Gorman MP, Dies KA, Robbins M, Hundley R, Wu B, Sahin M Abstract Distal partial trisomies involving the region 1q32 have been associated with dysmorphic features and developmental delay [1-11]. To further define the critical region for developmental delay and to investigate the genotype-phenotype association of 1q trisomy syndrome, we report two patients with much smaller (3 Mb and 3.5 Mb in size) trisomic regions on 1q32.1. The two micro-duplications largely overlap and both patients exhibited cognitive and motor delays. Case 1 is a 5-year-old boy with global developmental delay, behavioral problems, pervasive developmental disorder not otherwise specified (PDD-NOS), staring spells, headaches, and paresthesias. Case 2 is a 14-year-old girl wi... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5636040 Mon, 02 Jan 2012 05:00:00 +0100 5636040 http://www.medworm.com/index.php?rid=5636039&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22269966%26dopt%3DAbstract We report a prenatal case of a large 5p duplication with sub-telomeric deletion in a foetus with very mild phenotypic abnormalities. Foetal ultrasonographic examination at 22 weeks of gestation showed short femur, clubfeet, pielectasy, and facial dysmorphisms. Chromosome investigations revealed an inverted duplication of the short arm of chromosome 5 from 5p13.1 to 5p15.33 and a 800 kb deletion at 5pter. The absence of severe anomalies such as cardiac and cerebral defects, observed so far in all large 5p duplications, and the comparison to previous cases described both in literature and in DECIPHER database suggest that the critical region for the severe phenotype in 5p duplication syndrome might be smaller than that previously described, excluding half of the 5p13 band. This might help i... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5636039 Mon, 02 Jan 2012 05:00:00 +0100 5636039 http://www.medworm.com/index.php?rid=5617800&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245518%26dopt%3DAbstract Authors: Bashir R, Fatima A, Naz S Abstract Mutations in MYO15A are associated with deafness in humans, and shaker 2 mice also exhibit a hearing loss due to defects of unconventional myosin 15a. We ascertained a consanguineous Pakistani family with recessively inherited moderate to severe hearing loss, which putatively segregated with markers linked to the DFNB3 locus. Prioritized sequencing of the second exon of MYO15A from the DNA of all affected individuals of family revealed a duplication of Cytosine in a stretch of seven repetitive C nucleotides (c.1185dupC). This mutation results in a frameshift and incorporates a stop codon in the open reading frame of MYO15A (p.E396fsX431). The findings of less severe hearing loss in families with linkage to DFNB3 are only reported for some... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5617800 Fri, 30 Dec 2011 05:00:00 +0100 5617800 http://www.medworm.com/index.php?rid=5617799&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245519%26dopt%3DAbstract We report a 5-year-old boy with thiazide-resistant Bartter syndrome. This is highly unusual since thiazide hypersensitivity is a common diagnostic finding in Bartter syndrome patients. Subsequent molecular testing identified compound heterozygosity for two novel mutations in KCNJ1, (c.556A > G and c.683G > A) which is associated with Bartter syndrome, and a paternally inherited polymorphism in SLC12A3 (c.791G > C). Mutations in SLC12A3 cause the thiazide-resistant tubulopathy Gitelman syndrome. Based on published studies of this polymorphism in SLC12A3 and the features of the proband's father, we postulate that this polymorphism modifies the phenotype of Bartter syndrome in the proband to thiazide resistance. PMID: 22245519 [PubMed - as supplied by publisher] (Source: Eu... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5617799 Fri, 30 Dec 2011 05:00:00 +0100 5617799 http://www.medworm.com/index.php?rid=5594200&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226660%26dopt%3DAbstract We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, laparoschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS. PMID: 22226660 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetic... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5594200 Thu, 22 Dec 2011 05:00:00 +0100 5594200 http://www.medworm.com/index.php?rid=5574888&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22212417%26dopt%3DAbstract Authors: Graham JM Abstract Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point i... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5574888 Tue, 20 Dec 2011 05:00:00 +0100 5574888 http://www.medworm.com/index.php?rid=5574889&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22210230%26dopt%3DAbstract Authors: Ballarati L, Cereda A, Caselli R, Maitz S, Russo S, Selicorni A, Larizza L, Giardino D Abstract We identified a 495 Kb interstitial deletion of chromosome Xp22.2, centered on the AP1S2 gene, by means of oligonucleotide array comparative genomic hybridisation (array-CGH) in a child with marked hypotonia in the first months of life, psychomotor retardation, severely delayed walking and speech development, and unspecific dysmorphic facial features. The deletion was inherited from the healthy mother. Point mutations of the AP1S2 gene have been identified in patients with X-linked mental retardation (XLMR). The clinical features of our patient are quite similar to those reported in male patients carrying point mutations, thus suggesting that point mutations and deletions of th... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5574889 Sat, 17 Dec 2011 05:00:00 +0100 5574889 http://www.medworm.com/index.php?rid=5557591&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22200646%26dopt%3DAbstract Authors: Wooderchak-Donahue W, Stevenson DA, McDonald J, Grimmer JF, Gedge F, Bayrak-Toydemir P Abstract RASA1 mutations have been reported to be associated with hereditary capillary malformations (CM) with or without arteriovenous malformations (AVM), arteriovenous fistulas (AVF), or Parkes Weber syndrome. But the number of cases with RASA1 mutations reported to date is relatively small and the spectrum of phenotypes caused by mutations in this gene is not well defined. Mutation results and clinical findings in thirty-five unrelated consecutive cases sent for RASA1 molecular sequencing testing at ARUP Laboratories within the last two years were evaluated. Eight individuals had a pathogenic RASA1 mutation of which six were novel. These eight individuals all had CMs (seven had multi... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5557591 Thu, 08 Dec 2011 05:00:00 +0100 5557591 http://www.medworm.com/index.php?rid=5557590&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22201559%26dopt%3DAbstract We report here on a child affected by TAR syndrome associated with Langerhans cell histiocytosis. Unexpectedly, he showed a 2.029 kb deletion at 1q21.1, almost twice that of the unaffected mother (957 kb). Interestingly, the mother-to-son increased size of the deleted region was already observed in two cases of constitutional diseases, although both resulting as chromosomal terminal deletions. Noteworthy, qPCR experiments, never before performed for patients with TAR syndrome, disclosed that the proband had a statistically significant downregulation of the majority of the genes mapping inside the part of the deletion shared with the mother. The mother, on the contrary, did not show the same downregulation. In summary, the present report adds new insights on the pathogenesis of TAR syndro... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5557590 Thu, 08 Dec 2011 05:00:00 +0100 5557590 http://www.medworm.com/index.php?rid=5543671&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198201%26dopt%3DAbstract We report on a boy presenting with features of OAVS (Oculoauriculovertebral spectrum) and carrying a 1.5 Mb microdeletion in 15q24.1q24.2. This recurrent deletion usually leads to a broad clinical spectrum but has never been found associated with features of OAVS such as ear agenesis. This observation is in accordance with OAVS being a genetically heterogeneous disorder, and points out the importance of array-CGH screening in this disorder. PMID: 22198201 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5543671 Sat, 03 Dec 2011 05:00:00 +0100 5543671 http://www.medworm.com/index.php?rid=5543673&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186213%26dopt%3DAbstract In this report, we describe a 7 years old male with mental retardation, cryptorchid testes, short stature and alopecia carrying only an interstitial de novo deletion of 911 Kb in the 1q43 region (239,597,095-240,508,817) encompassing three genes CHRM3, RPS7P5 and FMN2. PMID: 22186213 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5543673 Fri, 02 Dec 2011 05:00:00 +0100 5543673 http://www.medworm.com/index.php?rid=5543672&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22193390%26dopt%3DAbstract We report here a child with a ring chromosome 5 (r(5)) associated with facial dysmorphology and multiple congenital abnormalities. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones was performed to determine the breakpoints involved in the r(5). The 5p deletion extended from 5p13.2-3 to 5pter and measured 34.61 Mb (range: 33.7-35.52 Mb) while the 5q deletion extended from 5q35.3 to 5qter and measured 2.44 Mb (range: 2.31-2.57 Mb). The patient presented signs such as microcephaly, hypertelorism, micrognathia and epicanthal folds, partially recalling those of a deletion of the short arm of chromosome 5 and the "cri-du-chat" syndrome. The most striking phenotypic features were the congenital heart abnormalities which have been frequently reported ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5543672 Fri, 02 Dec 2011 05:00:00 +0100 5543672 http://www.medworm.com/index.php?rid=5523537&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22178368%26dopt%3DAbstract This study reports two sisters from a consanguineous Lebanese family with an autosomal recessive Robinow syndrome. Both presented with short stature, dysmorphic facial features, and mild bone abnormalities. One of the affected girls had a malformation of her right hand: a mesoaxial polydactyly combined with a syndactyly of the 3rd and 4th fingers, and a short right 3rd metacarpal bone. Molecular analysis of the ROR2 gene revealed the presence of a previously undescribed missense mutation: p.R272C (c.814Cgt; T), in the cysteine-rich domain of the protein. These patients are compared with other cases, and a phenotype-genotype correlation is discussed. PMID: 22178368 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5523537 Sun, 27 Nov 2011 05:00:00 +0100 5523537 http://www.medworm.com/index.php?rid=5486848&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138216%26dopt%3DAbstract Authors: Verhoeven WM, Egger JI, Feenstra I, de Leeuw N Abstract A female patient, nine years of age, is reported with a history characterized by delay of psychomotor and speech development, mild to moderate intellectual disability and persistent sleep disturbances since the age of two. The patient showed facial dysmorphisms, a pectus excavatum and a sandal gap. Apart from lowered intelligence, neuropsychological functioning disclosed impaired attentional capacities and executive control as well as weak motor skills. Genome wide SNP array analysis revealed a 3.57 Mb de novo microdeletion in band q12.3 of chromosome 8. The long lasting sleep disorders turned out to originate from a rare juvenile epilepsy, continuous spike-waves during slow sleep (CSWS) syndrome, that includes the e... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5486848 Sun, 27 Nov 2011 05:00:00 +0100 5486848 http://www.medworm.com/index.php?rid=5486847&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22138217%26dopt%3DAbstract Authors: Szakszon K, Felszeghy E, Csízy I, Józsa T, Káposzta R, Balogh E, Oláh E, Balogh I, Berényi E, Knegt AC, Ilyés I Abstract Solitary Median Maxillary Central Incisor Syndrome (SMMCI) is a rare malformation syndrome consisting of multiple, mainly midline defects. Some authors suggest that it is a mild manifestation of the wide spectrum of holoprosencephaly, others classify it rather as a distinct entity. Authors report a case of SMMCI presenting with growth retardation, mild intellectual disability and absence of puberty. Cytogenetic and molecular cytogenetic investigations could identify no abnormalities. The presence of a single maxillary incisor called for further investigations to clarify hidden anomalies, these were empty sella, panhypopituitarism, hypothyroidism, a... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5486847 Thu, 17 Nov 2011 05:00:00 +0100 5486847 http://www.medworm.com/index.php?rid=5408377&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22080113%26dopt%3DAbstract We report a male patient, offspring of a consanguineous marriage between first cousins, with cognitive impairment, autistic-like behavior, deafness, postaxial polydactyly, and mild dysmorphic features. aCGH revealed a 600 kb homozygous deletion of 4p15.1 (from 33.553 to 34.159 Mb in NCBI36 hg18) encoding several transcripts of unknown function. Both parents are heterozygous for the deletion and the non-affected brother is homozygous for the normal alleles. We hypothesize that this deletion is likely to contribute to the phenotype of the patient. This case underlines the contribution of aCGH in discovering potentially pathogenic CNVs in consanguineous matings. PMID: 22080113 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5408377 Wed, 09 Nov 2011 05:00:00 +0100 5408377 http://www.medworm.com/index.php?rid=5408378&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22067610%26dopt%3DAbstract We report on a de novo intragenic deletion of the BMPR1A gene in a normally developing adolescent boy with short stature, delayed puberty, facial dysmorphism and an atrioventricular septal defect. Based on this finding, complemented with computational prioritization data and molecular evidence in literature, the critical region for CHD on 10q23 can be downsized to a single gene, BMPR1A. Although loss-of-function mutations in BMPR1A typically result in juvenile polyposis syndrome, none of the patients with the typical 10q22q23 microdeletion syndrome, comprising this gene, were reported to have juvenile polyposis thus far. We reason that, even in the absence of juvenile polyposis syndrome, sequencing and copy number analysis of BMPR1A should be considered in patients with (atrioventricular) ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5408378 Thu, 20 Oct 2011 04:00:00 +0100 5408378 http://www.medworm.com/index.php?rid=5408379&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22061479%26dopt%3DAbstract This report provides further evidence of phenotype-genotype correlation and expands the phenotypic spectrum of midline defects described with this syndrome. PMID: 22061479 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5408379 Wed, 19 Oct 2011 04:00:00 +0100 5408379 http://www.medworm.com/index.php?rid=5373392&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22044576%26dopt%3DAbstract Authors: Reutter H, Bagci S, Müller A, Gembruch U, Geipel A, Berg C, Eggermann T, Spengler S, Bartmann P, Rudnik-Schöneborn S Abstract Here we describe a patient with a new malformation syndrome which shows similarities with Yunis-Varon syndrome (YVS). Prenatal presentation included polyhydramnios, increased nuchal translucency, and bilateral hydrothoraces requiring pigtail insertion. Postnatal presentation revealed primary pulmonary hypertension (PPH), persistent hydrothoraces, one atrial and two ventricular septal defects, hypoplasia of the corpus callosum and cerebellar vermis, dilated interhemispheric ventricles, severe developmental delay with general muscular hypotonia, retinal anomalies, sparse scalp hair, sparse eyebrows and eyelashes, hypo- and aplastic nails, low-set dy... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5373392 Tue, 11 Oct 2011 04:00:00 +0100 5373392 http://www.medworm.com/index.php?rid=5293208&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21971480%26dopt%3DAbstract We report a new case of 8q interstitial duplication in a patient with dysmorphic features, umbilical hernia, cryptorchidism, short stature, congenital heart defect and mild mental retardation (MR). Chromosome analysis with high resolution QFQ bands showed 46,XY, 8q+, which was interpreted as a partial duplication of the distal long arm of chromosome 8 (q22 → qter). This chromosomal aberration was further characterized using fluorescence in situ hybridization (FISH) analyses with multiple DNA probes and array-CGH (Comparative Genomic Hybridization) experiment which demonstrated a de novo direct duplication (8)(q22.2-q24.3). We have compared this case with other partially trisomic 8q patients reported in literature and highlighted the common clinical features in 8q22-8q24 duplication syn... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5293208 Sun, 25 Sep 2011 04:00:00 +0100 5293208 http://www.medworm.com/index.php?rid=5293209&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21968327%26dopt%3DAbstract Authors: Yuca SA, Rendtorff ND, Boulahbel H, Lodahl M, Tranebjærg L, Cesur Y, Dogan M, Yilmaz C, Akgun C, Acikgoz M Abstract Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1 region. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients show... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5293209 Fri, 23 Sep 2011 04:00:00 +0100 5293209 http://www.medworm.com/index.php?rid=5272325&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21958693%26dopt%3DAbstract In conclusion, one should consider the possibility of CTX in any individual with normocholesterolemic xanthomatosis, early-onset cataracts, mental retardation, cerebellar ataxia and peripheral neuropathy. PMID: 21958693 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5272325 Fri, 16 Sep 2011 04:00:00 +0100 5272325 http://www.medworm.com/index.php?rid=5256195&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21933724%26dopt%3DAbstract We report a family with an apparent XLID pattern with the proband, his mother and maternal half brother having an Xp21.3 deletion detected with chromosomal microarray analysis involving the interleukin 1 receptor accessory protein-like 1 (IL1RAPL1) gene. IL1RAPL1 is highly expressed in the postnatal brain, specifically hippocampus suggesting a specialized role in memory and learning abilities. The proband presented with intellectual disability, a broad face, prominent and wide nasal root, ptosis, a wide philtrum and a small mouth. XLID due to involvement of the IL1RAPL1 gene has been reported to cause nonsyndromic XLID. We report a new family with XLID due to partial deletion of IL1RAPL1, summarize reported literature and describe similar phenotypic similarities among the affected individu... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5256195 Sat, 10 Sep 2011 04:00:00 +0100 5256195 http://www.medworm.com/index.php?rid=5224427&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21914491%26dopt%3DAbstract We report on the prenatal diagnosis of a ring chromosome 10 in a fetus in which talipes equinovarus was incidentally found during routine obstetric ultrasound at 22 weeks of gestation. Amniocentesis was undertaken and cytogenetic analysis revealed a de novo non-mosaic apparently stable ring chromosome 10 replacing one of the two homologs. Multiplex Ligation-dependent Probe Amplification (MLPA) revealed subtelomeric deletions in both the short and long arm of chromosome 10. Analysis with high resolution micro-array based comparative genomic hybridization (array-CGH), defined the ring chromosome as del 10p15.3-p14 (12.59Mb in size) and del 10q26.3 (4.22Mb in size) and revealed the genes that are deleted. After elected termination of the pregnancy at 27th week of gestation a detailed autopsy ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5224427 Fri, 09 Sep 2011 04:00:00 +0100 5224427 http://www.medworm.com/index.php?rid=5214613&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893220%26dopt%3DAbstract Authors: Bartsch O, Schindler D, Beyer V, Gesk S, Van't Slot R, Feddersen I, Buijs A, Jaspers NG, Siebert R, Haaf T, Poot M Abstract A 9-year-old girl born to healthy parents showed manifestations suggestive of ataxia telangiectasia (AT), such as short stature, sudden short bouts of horizontal and rotary nystagmus, a weak and dysarthric voice, rolling gait, unstable posture, and atactic movements. She did not show several cardinal features typical of AT such as frequent, severe infections of the respiratory tract. In contrast, she showed symptoms not generally related to AT, including microcephaly, profound motor and mental retardation, small hands and feet, severely and progressively reduced muscle tone with slackly protruding abdomen and undue drooling, excess fat on her upper ar... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5214613 Sat, 27 Aug 2011 04:00:00 +0100 5214613 http://www.medworm.com/index.php?rid=5214614&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21888995%26dopt%3DAbstract Authors: Laurence J, Vincent C, Sébastien P, Malek L, Souad G, Françoise D, Sandrine M Abstract In 2008, SLC29A3 has been implicated in a syndromic form of genodermatosis: H syndrome. The major features encountered in H syndrome are Hearing loss, Hyperglycaemia, Heart anomalies, Hypertrichosis, Hyperpigmentation, Hepatomegaly and Hypogonadism. More recently, SLC29A3 mutations have been described in families presenting syndromes associating generalized histiocytosis to systemic progressive features: severe camptodactyly, hearing loss, hypogonadism, hepatomegaly, heart defect and skin hyperpigmentation. We have identified a homozygous missense SLC29A3 mutation in a patient presenting with only a progressive sensorineural hearing impairment and a single cervical node. SLC29A3 mutati... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5214614 Tue, 23 Aug 2011 04:00:00 +0100 5214614 http://www.medworm.com/index.php?rid=5183977&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21872685%26dopt%3DAbstract This report confirms that neutrophil count should be performed in all patients with poikiloderma to target the C16orf57 gene sequencing analysis, prior to RECQL4 analysis. PMID: 21872685 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5183977 Wed, 17 Aug 2011 23:00:00 +0100 5183977 http://www.medworm.com/index.php?rid=5147035&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21846512%26dopt%3DAbstract Authors: Millat G, Bouvagnet P, Chevalier P, Sebbag L, Dulac A, Dauphin C, Jouk PS, Delrue MA, Thambo JB, Le Metayer P, Seronde MF, Faivre L, Eicher JC, Rousson R Abstract Dilated Cardiomyopathy (DCM) is one of the leading causes of heart failure with high morbidity and mortality. More than 30 genes have been reported to cause DCM. To provide new insights into the pathophysiology of dilated cardiomyopathy, a mutational screening on 4 DCM-causing genes (MYH7, TNNT2, TNNI3 and LMNA) was performed in a cohort of 105 unrelated DCM (64 familial cases and 41 sporadic cases) using a High Resolution Melting (HRM)/sequencing strategy. Screening of a highly conserved arginine/serine (RS)-rich region in exon 9 of RBM20 was also performed. Nineteen different mutations were identified in 20 ind... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5147035 Wed, 03 Aug 2011 23:00:00 +0100 5147035 http://www.medworm.com/index.php?rid=5147036&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843665%26dopt%3DAbstract Authors: Lu Y, Liu YZ, Liu PY, Dvornyk V, Deng HW Abstract A common purpose of microarray experiments is to study the variation in gene expression across the categories of an experimental factor such as tissue types and drug treatments. However, it is not uncommon that the studied experimental factor is a quantitative variable rather than categorical variable. Loss of information would occur by comparing gene-expression levels between groups that are factitiously defined according to the quantitative threshold values of an experimental factor. Additionally, lack of control for some sensitive clinical factors may bring serious false positive or negative findings. In the present study, we described a bootstrap-based regression method for analyzing gene-expression data from the non-ca... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5147036 Fri, 29 Jul 2011 23:00:00 +0100 5147036 http://www.medworm.com/index.php?rid=5133645&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21839187%26dopt%3DAbstract Authors: Verhagen JM, Schrander-Stumpel CT, Krapels IP, de Die-Smulders CE, van Lint FH, Willekes C, Weber JW, Gavilanes AW, Macville MV, Stegmann AP, Engelen JJ, Bakker J, Vos YJ, Frints SG Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Clinical Genetics between 1985 and 2010 by perinatologists, (pediatric) neurologists or pediatricians. Patients with hydrocephalus secondary to other pathology were excluded from this survey. We classified patients with primary congenital hydrocephalus into two main groups: non-syndromic hydrocephalus (NSH)... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5133645 Fri, 29 Jul 2011 23:00:00 +0100 5133645 http://www.medworm.com/index.php?rid=5133649&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816241%26dopt%3DAbstract The objective of this study was to check whether DFNB66 and DFNB67 are distinctive loci and determining their contribution to HL. In the DFNB66 family, sequencing showed absence of mutations in the untranslated regions and the predicted promoter sequence of LHFPL5. Analysis of five microsatellites in the 6p21.31-22.3 region and screening of the LHFPL5 gene by DNA heteroduplex analysis in DHPLC revealed a novel mutation (c.89dup) in one out of 129 unrelated Tunisian families with autosomal recessive nonsyndromic (ARNS) HL. Our findings suggest that two distinct genes are responsible for DFNB66 and DFNB67 HL. These loci are likely to be a rare cause of ARNSHL. PMID: 21816241 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5133649 Mon, 25 Jul 2011 23:00:00 +0100 5133649 http://www.medworm.com/index.php?rid=5133651&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816240%26dopt%3DAbstract We describe here the first report from India wherein, two cases of 46,XY complete gonadal dysgenesis that could be attributable to mutations in the Desert hedgehog (DHH) gene. The mutations found in these two patients were a homozygous deletion (c.271_273delGAG) that resulted in deletion of one amino acid (p.D90del) and a homozygous duplication (c.57-60dupAGCC) that resulted in premature termination resulting in non-functional DHH protein. The structure-function implications of the p.D90del mutation were predicted using computational tools. Structural studies on the p.D90del mutant revealed that the mutation could seriously perturb the interaction of DHH with its binding partners. This is the second report in literature showing homozygous mutation in cases with 46,XY complete gonadal dysge... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5133651 Fri, 22 Jul 2011 23:00:00 +0100 5133651 http://www.medworm.com/index.php?rid=5133652&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816239%26dopt%3DAbstract We describe the clinical characteristics of 4 singleton cases, 3 males and 1 female, with Myhre Syndrome (OMIM 139210), who were born to non-consanguineous parents. Three cases had no family history of similarly affected individuals but 1 male's mother had short stature, some facial features suggestive of Myhre syndrome and evidence of skewed X-chromosome inactivation in her blood DNA. Short stature, deafness, learning difficulties, skeletal anomalies and facial dysmorphisms were evident in all cases. Arthralgia and stiff joints with limited movement were also present. The facial appearance, thickened skin, a 'muscular' habitus are memorable features. The female patient was least affected: this patient and one affected male displayed streaky skin with areas of patchy thickening, suggestive... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5133652 Wed, 20 Jul 2011 23:00:00 +0100 5133652 http://www.medworm.com/index.php?rid=5133646&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21816242%26dopt%3DAbstract CONCLUSION: The results of our study show the association of polymorphisms rs9356058 and rs1040079 in gene PARK2/PACRG with leprosy. The results of our study indicate that exposure to leprosy and mortality in the population caused by leprosy on Mljet resulted in the selection of rs9356058 "protective" C allele in the PARK2 gene, while this was not observed in the two control groups. This is the first study to assess the genetic susceptibility to leprosy in a European population. PMID: 21816242 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5133646 Sun, 17 Jul 2011 23:00:00 +0100 5133646 http://www.medworm.com/index.php?rid=5086849&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21787890%26dopt%3DAbstract CONCLUSION: To our knowledge this is the first non-peripheral myelin protein 22 copy number variation to cause Charcot-Marie-Tooth disease. PMID: 21787890 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086849 Sun, 17 Jul 2011 23:00:00 +0100 5086849 http://www.medworm.com/index.php?rid=5086848&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21791255%26dopt%3DAbstract Authors: Gonzalez-Quereda L, Delgadillo V, Juan-Mateu J, Verdura E, Rodriguez MJ, Baiget M, Pineda M, Gallano P Hutchinson-Gilford progeria syndrome is a very rare but well-characterized genetic disorder that causes premature ageing. Clinical features affect growth, skeleton, body fat, skin, hair and the cardiovascular system. It is caused by mutations in LMNA gene, the most frequent being p.Gly608Gly (c.1824C > T) in exon 11. Here we present a four-year-old HGPS patient who presented several severe strokes and carried a heterozygous LMNA missense mutation in exon 2: p.Glu138Lys. This mutation is located far from the C-terminal region implicated in the posttranslational processing of prelamin A, but it lies within the rod domain of lamin A/C that represents a highly conserved doma... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086848 Sun, 17 Jul 2011 23:00:00 +0100 5086848 http://www.medworm.com/index.php?rid=5086850&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782985%26dopt%3DAbstract We report on a microduplication identified by array-CGH (comparative genomic hybridization) including five contiguous genes (OPHN1, YIPF6, STARD8, EFNB1 and PJA1) and arising de novo in a male presenting a congenital diaphragmatic hernia (CDH). Our case is the second report of EFNB1 duplication associated with CDH in a male patient, supporting its implication sensitive to gene dosage in diaphragm development. PMID: 21782985 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086850 Wed, 13 Jul 2011 23:00:00 +0100 5086850 http://www.medworm.com/index.php?rid=5086847&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21802533%26dopt%3DAbstract In this study, we report a novel mutation (p.Y305H) in the ESRRB gene in a Tunisian family with ARNSHL. This mutation was not detected in 100 healthy individuals. Molecular modeling showed that the p.Y305H mutation is likely to alter the conformation of the ligand binding-site by destabilizing the coactivator binding pocket. Interestingly, this ligand-binding domain of the ESRRB protein has been affected in 5 out of 6 mutations causing DFNB35 hearing loss. Using linkage and DHPLC analysis, no more mutations were detected in the ESRRB gene in other 127 Tunisian families with ARNSHL indicating that DFNB35 is most likely to be a rare type of ARNSHL in the Tunisian population. PMID: 21802533 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086847 Tue, 12 Jul 2011 23:00:00 +0100 5086847 http://www.medworm.com/index.php?rid=5086852&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777705%26dopt%3DAbstract Authors: Zahnleiter D, Trautmann U, Ekici AB, Goehring I, Reis A, Dörr HG, Rauch A, Thiel CT We identified a maternally inherited 14.2Mb duplication 5q22.1-q23.2 in two female siblings and their mother by molecular karyotyping. Both siblings were small for gestational age and presented with pronounced postnatal growth retardation, mild motor delay, congenital heart disease in one of the siblings, and distinct facial dysmorphism. As this duplication is one of the smallest reported 5q duplications, short stature and facial dysmorphism can be attributed to duplications of 5q22, whereas severe mental retardation is not part of the phenotypic spectrum of the 5q22.1-q23.2 region. Congenital heart defects, as observed in other 5q duplications, have a variable penetrance. We compared the faci... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086852 Mon, 11 Jul 2011 23:00:00 +0100 5086852 http://www.medworm.com/index.php?rid=5086851&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21782042%26dopt%3DAbstract Authors: Brison N, Tylzanowski P, Debeer P Synpolydactyly (SPD) is a rare congenital limb disorder caused by mutations in the HOXD13 gene, a homeobox transcription factor crucial for autopod development. The hallmarks of SPD are the webbing between the third and the fourth finger and the fourth and the fifth toe, with a partial or complete digit duplication in the syndactylous web. Different classes of HOXD13 mutations are involved in the pathogenesis of synpolydactyly, but an unequivocal genotype-phenotype correlation cannot always be achieved due to the lack of structure-function data of HOXD13. Mutations in DNA binding or polyalanine tract domains of HOXD13 result in predictable clinical outcomes. However, mutations outside of these domains cause a broad variety of clinical features... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=5086851 Fri, 01 Jul 2011 23:00:00 +0100 5086851 http://www.medworm.com/index.php?rid=4993448&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21689796%26dopt%3DAbstract We report the detailed clinical features, as well as refine the rearrangement breakpoints of this disease-associated copy number variation region, which encompasses more than 50 genes. We propose that in addition to ID, the phenotypic spectrum associated with dup(X)(p11.22-p11.23) can include ASD, language impairment, and/or other primary psychiatric disorders. PMID: 21689796 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4993448 Mon, 27 Jun 2011 23:00:00 +0100 4993448 http://www.medworm.com/index.php?rid=4993445&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21708297%26dopt%3DAbstract Authors: De Marco P, Raso A, Beri S, Gimelli S, Merello E, Mascelli S, Baldi M, Baffico AM, Pavanello M, Cama A, Capra V, Giorda R, Gimelli G Saethre-Chotzen syndrome (SCS) is an autosomal dominant craniosynostosis syndrome with variable expression. Here we report on a female infant with a de novo balanced translocation 46, XX, t(7;12)(p21.2;p12.3) and presenting at birth brachycephaly, antimongolic palpebral fissures, ocular hypertelorism, broad nose with low nasal bridge and low-set ears. This phenotype is suggestive of a subtle form of SCS, given the absence of limbs anomalies. Cloning of both breakpoints revealed that the translocation does not interrupt the TWIST1 coding region, on 7p21, known to be causative for SCS, but downregulates TWIST1 expression due to a position effect. O... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4993445 Thu, 23 Jun 2011 23:00:00 +0100 4993445 http://www.medworm.com/index.php?rid=4993449&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684358%26dopt%3DAbstract We report on a family with syndromic X-linked mental retardation (XLMR) caused by an Xp22.2-22.13 duplication. This family consists of a carrier mother and daughter and four affected sons, presenting with mental retardation, developmental delay, cardiovascular problems and mild dysmorphic facial features. Female carriers have normal intelligence and some common clinical features, as well as different clinical abnormalities. Cytogenetic analysis of the mother showed an Xp22.2 duplication which was passed to all her offspring. Fluorescence In Situ Hybridization (FISH) using whole chromosome paint and Bacterial Artificial Chromosome (BAC) clones covering Xp22.12-Xp22.3 region, confirmed the X chromosome origin and the size of the duplication. Two different targeted microarray methodologies we... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4993449 Thu, 16 Jun 2011 23:00:00 +0100 4993449 http://www.medworm.com/index.php?rid=4993447&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21700001%26dopt%3DAbstract Authors: Mosrati MA, Hammami B, Rebeh IB, Ayadi L, Dhouib L, Khaireddine BM, Hakim B, Charfeddine I, Jameleddine M, Ghorbel A, Masmoudi S Branchio-oto-renal (BOR) and Branchio-otic (BO) syndromes are dominant disorders characterized by variable hearing impairment (HI) and branchial defects. BOR includes additional kidney malformations. BO/BOR syndromes are genetically heterogeneous and caused by mutations in EYA1 and SIX1 genes. Mutation in SIX1 is responsible also for DFNA23, a locus for non-syndromic HI. Strikingly, the severity of the phenotype did not seem to correlate with the type of SIX1 mutation. Herein, we identified a novel mutation in SIX1 (p.E125K) in a Tunisian family with variable HI and preauricular pits. This mutation is located at the same position as the mutation iden... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4993447 Tue, 14 Jun 2011 23:00:00 +0100 4993447 http://www.medworm.com/index.php?rid=4993446&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21700002%26dopt%3DAbstract We describe a 3.5 year old girl presenting with short stature, developmental delay, marked muscular hypotonia with ataxia, premature pubarche, and dysmorphic features. A 1.07-1.12Mb-sized de novo microdeletion of chromosome 19p13.11 is most likely the cause for the clinical phenotype. The patient did not show any abnormalities of the extremities which contrasts with the finding of one previously reported patient with an overlapping deletion presenting with split hand and foot malformation (SHFM). The remarkable difference is that in the previously described patient but not in the patient reported herein the genes EPS15L1 and CALR3 were deleted. As EPS15L1 has been associated with limb development previously, the presented case provides indirect evidence that this may be a new candidate gen... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4993446 Mon, 06 Jun 2011 23:00:00 +0100 4993446 http://www.medworm.com/index.php?rid=4944575&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664500%26dopt%3DAbstract In this study we present three new cases with such a mosaicism, which were detected by Single Nucleotide Polymorphism (SNP) array analysis in our routine diagnostic setting. These cases were further characterized using Fluorescence in situ Hybridisation (FISH) analysis and conventional karyotyping. The first case is a mentally retarded male who carries an unbalanced translocation in 87% of his cells. The phenotypically normal mother carries the balanced form of the translocation in all her cells. The second case is a phenotypically normal female who has an unbalanced translocation in 52% of her cells. The inheritance could not be determined. The third case is a female referred for Rubinstein-Taybi syndrome who carries an unbalanced translocation in 60% of her cells. Both parents of this ca... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4944575 Sun, 22 May 2011 23:00:00 +0100 4944575 http://www.medworm.com/index.php?rid=4944574&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21664501%26dopt%3DAbstract Authors: Keller S, Prechtl D, Aslanidis C, Ceglarek U, Thiery J, Schmitz G, Jahreis G Whilst conducting a scientific study, an elevated plasma plant sterol concentration of 3.07 mg/dL was established in one proband. Similar levels found in his mothers plasma (2.73 mg/dL) were suggestive of a heterozygous sitosterolemia. The resulting gene analysis for ATP binding cassette transporter G5/G8 (ABCG5/G8) revealed a heterozygous polymorphism in ABCG8 (Thr400Lys, rs4148217), which the proband had inherited from his father. However, a heterozygous amino acid exchange (Arg406Gln) in exon 9 of ABCG5 was revealed, which was inherited from his mother. Although not sufficient evidence exists to regard this sequence variation as a mutation, this previously unreleased sequence variation occurred i... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4944574 Sun, 22 May 2011 23:00:00 +0100 4944574 http://www.medworm.com/index.php?rid=4894166&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21635976%26dopt%3DAbstract We report the result of a French multicentric clinical study, and we emphasized on the role of the associated 1q21.1 deletion in the diagnosis and the genetic counselling of our patients. We gathered information on 14 patients presenting with TAR syndrome and referred for genetic counselling in six different university hospitals (8 foetuses, 1 child and 5 adults). Clinical or pathology details, as well as skeletal X-rays were analyzed. Genetic studies were performed by Array-CGH, and Quantitative Multiplex PCR. We demonstrated the very variable phenotypes of TAR syndrome. Female:male ratio was ∼2:1. All patients presented with bilateral radial aplasia/hypoplasia with preserved thumbs. Phocomelia and lower limb anomalies were present in 28% of the cases. We reported the first case of cyst... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4894166 Thu, 12 May 2011 23:00:00 +0100 4894166 http://www.medworm.com/index.php?rid=4894167&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21621018%26dopt%3DAbstract This report supports the previous observations assuming that severity of phenotype in patients with inv dup(15) depends on the dosage of the PWACR and that skin pigmentation is correlated to OCA2 gene copy number. PMID: 21621018 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4894167 Thu, 05 May 2011 23:00:00 +0100 4894167 http://www.medworm.com/index.php?rid=4894168&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21616179%26dopt%3DAbstract Authors: Chen GW, Luo X, Liu YL, Jiang Q, Qian XM, Guo ZY Insulin-like peptide 6 (INSL6) is a newly identified insulin/relaxin family peptide hormone that is predominantly expressed by the male germ cells in testes. A recent murine study demonstrated that INSL6-knockout results in spermatogenic failure. In the present study, human INSL6 gene was screened for mutations that may contribute to human spermatogenic failure. Of 249 patients and 249 healthy control subjects, a heterozygous R171H missense mutation was found in one patient. The R171H mutation probably disturbed the in vivo processing of the INSL6 prohormone because it was located at the absolutely conserved tetrabasic cleavage site between the C-peptide and the A-chain, therefore the R171H missense mutation might be responsibl... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4894168 Tue, 03 May 2011 23:00:00 +0100 4894168 http://www.medworm.com/index.php?rid=4849079&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21571108%26dopt%3DAbstract We describe a family with a novel 1.8kb deletion that is associated with hypermethylation at IC1. The mutation results from recombination between highly homologous sequences containing target sites for the zinc-finger protein CTCF (CTSs). This finding supports the hypothesis that the function of IC1 and the penetrance of the clinical phenotype depend on the spacing of the CTSs resulting from recombination in the mutant allele. PMID: 21571108 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4849079 Tue, 03 May 2011 23:00:00 +0100 4849079 http://www.medworm.com/index.php?rid=4849074&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21596161%26dopt%3DAbstract Authors: Spielmann M, Reichelt G, Hertzberg C, Trimborn M, Mundlos S, Horn D, Klopocki E The heterozygous 15q13.3 microdeletion syndrome (MIM #612001) was first described by Sharp et al. in 2008. So far four patients with 15q13.3 homozygous or compound heterozygous microdeletions have been identified. Here we report a non-consanguineous family with two affected siblings carrying a homozygous microdeletion of ∼1.5 Mb at the 15q13.3 locus. They presented with congenital retinal dysfunction, refractory epilepsy, encephalopathy, mental retardation, repetitive hand movements, severe muscular hypotonia and macrocytosis. Dysmorphic facial features are synophrys and bilateral proptosis. The siblings carry a homozygous microdeletion at 15q13.3 of ∼1.5 Mb including the genes ARHGAP11B, M... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4849074 Thu, 28 Apr 2011 23:00:00 +0100 4849074 http://www.medworm.com/index.php?rid=4849093&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21558024%26dopt%3DAbstract Response to Dr. H. Rivera regarding article "21 Mb deletion in chromosome band 13q22.2-q32.1 associated with mild/moderate psychomotor retardation, growth hormone insufficiency, short neck, micrognathia, hypotonia, dysplastic ears and other dysmorphic features" Eur J Med Genet. 2011 Apr 23; Authors: Patsalis PC PMID: 21558024 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4849093 Fri, 22 Apr 2011 23:00:00 +0100 4849093 http://www.medworm.com/index.php?rid=4794579&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21540131%26dopt%3DAbstract CONCLUSION: Our findings suggest a slight maternal contraction bias as opposed to a paternal expansion bias of the mutant HTT CAG repeat during intergenerational transmission, which only in the maternal line is associated with normal HTT CAG repeat size. PMID: 21540131 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794579 Fri, 22 Apr 2011 23:00:00 +0100 4794579 http://www.medworm.com/index.php?rid=4794578&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21540132%26dopt%3DAbstract Letter regarding the article: "21 Mb deletion in chromosome band 13q22.2-q32.1 associated with mild/moderate psychomotor retardation, growth hormone insufficiency, short neck, micrognathia, hypotonia, dysplastic ears and other dysmorphic features" by Grigori et al. Eur J Med Genet. 2011 Apr 23; Authors: Rivera H PMID: 21540132 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794578 Fri, 22 Apr 2011 23:00:00 +0100 4794578 http://www.medworm.com/index.php?rid=4794580&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21540130%26dopt%3DAbstract We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome. PMID: 21540130 [PubMed ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794580 Mon, 18 Apr 2011 23:00:00 +0100 4794580 http://www.medworm.com/index.php?rid=4794581&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524721%26dopt%3DAbstract Authors: Rué M, Lüdecke HJ, Sibon I, Richez C, Taine L, Foubert-Samier A, Arveiler B, Schaeverbeke T, Lacombe D, Tison F, Goizet C Sparse scalp hair, a peculiar shape of the nose, and cone-shaped epiphyses of the phalanges are the hallmarks of the tricho-rhino-phalangeal syndromes (TRPS). Short stature, hip dysplasia, and malformations of inner organs including mitral valve prolpase have also often been described for these conditions. Here, we described a 64-year-old woman with molecularly proved TRPS I and several atypical late-onset rheumatologic and neurological symptoms. PMID: 21524721 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794581 Thu, 14 Apr 2011 23:00:00 +0100 4794581 http://www.medworm.com/index.php?rid=4794582&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21477668%26dopt%3DAbstract Authors: Zhang H, Gao J, Ye J, Gong Z, Gu X The Cockayne syndrome is a rare autosomal recessive disease characterized by a general developmental delay, the unique face, and abnormal skin sensitivity to sunlight. It belongs to the family of disorders of the nucleotide excision repair system. Mutations of the ERCC6 and ERCC8 genes are the predominant cause of the Cockayne syndrome, whereby the ERCC6 gene mutation makes up approximately 70% of the cases. We report a Chinese case of a classic Cockayne syndrome, carrying the novel nonsense mutation c.1387C>T/Q463X in the ERCC6 gene in an apparently homozygous status. This mutation was found in a heterozygous status in this patient's father, while the mother carried two wild-type ERCC6 alleles. A further molecular investigation of the f... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794582 Tue, 05 Apr 2011 23:00:00 +0100 4794582 http://www.medworm.com/index.php?rid=4794584&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21473936%26dopt%3DAbstract This report demonstrates the remarkable intrafamilial variability of a 22q11.2 microduplication phenotype. The 22q11.2 microduplication carried by one of the healthy parents has most likely contributed to the recurrent fetal heart defects. PMID: 21473936 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794584 Mon, 04 Apr 2011 23:00:00 +0100 4794584 http://www.medworm.com/index.php?rid=4794583&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21473937%26dopt%3DAbstract CONCLUSION: The practice of medical genetics, involving prenatal genetic diagnosis of sickle cell disease and chromosomal anomalies, is possible in Cameroon (sub-Saharan Africa). PMID: 21473937 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4794583 Sun, 03 Apr 2011 23:00:00 +0100 4794583 http://www.medworm.com/index.php?rid=4684911&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466863%26dopt%3DAbstract Authors: Northup JK, Matalon R, Lockhart LH, Hawkins JC, Velagaleti GV Complex chromosome rearrangements (CCRs) are structural abnormalities involving >2 chromosomes or >3 breakpoints. It has been suggested that the probability of imbalance increases as the number of breakpoints increase. Here we report a 7-month-old, Hispanic girl presenting with cleidocranial dysplasia (CCD) who was found to have a complex chromosome rearrangement of chromosome 6. Fluorescence in situ hybridization studies with bacterial artificial chromosome (BAC) clones showed that the rearrangement involved insertion of 6q into 6p disrupting the "Runt related transcription factor 2 (RUNX2)" gene at chromosome 6p21.1. In addition, a pericentric inversion of chromosome 6 was identified. Despite the complex nat... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4684911 Fri, 01 Apr 2011 23:00:00 +0100 4684911 http://www.medworm.com/index.php?rid=4684913&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21457803%26dopt%3DAbstract Authors: Jehee FS, Takamori JT, Vasconcelos Medeiros PF, Pordeus AC, Latini FR, Bertola DR, Kim CA, Passos-Bueno MR PMID: 21457803 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4684913 Mon, 28 Mar 2011 23:00:00 +0100 4684913 http://www.medworm.com/index.php?rid=4684912&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21457804%26dopt%3DAbstract Authors: Zhang J, Han D, Song S, Wang Y, Zhao H, Pan S, Bai B, Feng H Mutations in the ectodysplasin-A (EDA) gene can cause both X-linked hypohidrotic ectodermal dysplasia (XLHED) and non-syndromic hypodontia (NSH). The correlation between the phenotypes and genotypes of these two conditions has yet to be described. In the present study, 27 non-consanguineous Chinese XLHED subjects were screened and 17 EDA mutations were identified. In order to investigate the correlation between genotype and phenotype, we also reviewed related studies on NSH subjects with confirmed EDA mutations and compared the differences in the clinical manifestations and EDA mutations of the two conditions. Tooth agenesis was observed in addition to abnormalities of other ectodermal organs. Tooth agenesis was more... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4684912 Mon, 28 Mar 2011 23:00:00 +0100 4684912 http://www.medworm.com/index.php?rid=4684914&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21440097%26dopt%3DAbstract We report on a patient with a Complex Chromosomal Rearrangement (CCR) of a chromosome 20. CCRs are structural rearrangements involving three or more chromosomes or having more than two breakpoints; congenital CCRs compatible with life are a rare finding in humans. The rearranged chromosome 20 was characterized by array Comparative Genomic Hybridisation (array CGH), and Fluorescent In Situ Hybridization (FISH). The combination of these two techniques made it possible to precisely define the rearrangement and showed a very unusual architecture, with segments deleted, duplicated, inverted, and shifted. Potential mechanisms generating such a complex rearrangement and candidate genes responsible for the phenotype are discussed. PMID: 21440097 [PubMed - as supplied by publisher] (Source: Eur... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4684914 Wed, 23 Mar 2011 00:00:00 +0100 4684914 http://www.medworm.com/index.php?rid=4628336&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21426945%26dopt%3DAbstract Authors: Gilling M, Lind-Thomsen A, Mang Y, Bak M, Møller M, Ullmann R, Kristoffersson U, Kalscheuer VM, Henriksen KF, Bugge M, Tümer Z, Tommerup N In a monozygotic twin couple with mental retardation (MR), we identified a maternally inherited inversion and a paternally inherited translocation: 46,XY,inv(10)(p11.2q21.2)mat,t(9;18)(p22;q21.1)pat. The maternally inherited inv(10) was a benign variant without any apparent phenotypical implications. The translocation breakpoint at 9p was within a cluster of interferon α genes and the 18q21 breakpoint truncated ZBTB7C (zinc finger and BTB containing 7C gene). In addition, analyses with array-CGH revealed a 931 kb maternally inherited deletion on chromosome 8q22 as well as an 875 kb maternally inherited duplication on 5p14. The deletion e... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628336 Sat, 19 Mar 2011 00:00:00 +0100 4628336 http://www.medworm.com/index.php?rid=4628343&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21420514%26dopt%3DAbstract In this study, we aimed to evaluate the impact on patients of sending them written information after a clinical consultation in a French genetics department. During a period of three months, two geneticists and one genetic counselor offered to send each patient a copy of the letter sent to their general practitioners. A questionnaire was sent with this copy. Three hundred and seventy-five patients were seen and 64% of the questionnaires were sent back. Of these, 99% showed that this practice was considered a good idea, and 80% reported that the letter reflected the clinical aspects well. Seventy-two percent thought that receiving this letter improved their understanding of the clinical situation. In general, patients found the words understandable (83%), too medical (20%) or even shocking ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628343 Thu, 17 Mar 2011 00:00:00 +0100 4628343 http://www.medworm.com/index.php?rid=4628338&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21420515%26dopt%3DAbstract Authors: Schwanitz G, Korsch E, Gamerdinger U, Heidrich-Kaul C, Schubert R, Spengler S, Kremens-Korsch U, Alhbory K, Eggermann T The clinical follow-up over 6 years and genetic testing results of a boy with mosaic tetrasomy 14q are reported [1].The motoric and psychological development of the patient could now be followed up over a period of 7 years and showed an increasing retardation. Repeated investigations of chromosomes and interphase FISH revealed no differences in the amount of aberrant cells from peripheral blood and buccal mucosa (20-25%) during the first 2 years of life of the patient and there were no differences between buccal mucosa from right and left side. Interestingly, within the last 5 years the amount of aberrant cells almost doubled in peripheral blood (40-48%). A c... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628338 Thu, 17 Mar 2011 00:00:00 +0100 4628338 http://www.medworm.com/index.php?rid=4628344&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21402185%26dopt%3DAbstract This report describes a Chinese family with SHS over three generations in which all affected individuals showed vertical talus and one demonstrated preauricular tags on the face. Linkage analysis and PCR sequencing revealed a novel substitute mutation at a hot-spot site in TNNT3 (c.187C>T; p.R63C). This mutation was confirmed to cosegregate with the DA phenotype in affected individuals. SIFT and PolyPhen analyses suggest that the mutation is pathogenic. We report this mutation in TNNT3 and speculate that bilateral vertical talus, or severe clubfoot, might be a special characteristic for cases with the TNNT3 R63C mutation. PMID: 21402185 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628344 Fri, 11 Mar 2011 00:00:00 +0100 4628344 http://www.medworm.com/index.php?rid=4628346&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397058%26dopt%3DAbstract We report a novel deletion encompassing the exons 5-12 of the UBE3A gene in a girl with AS, identified by MLPA (Multiplex Ligation-dependent Probe Amplification), which was not detected by the conventional diagnostic protocol. We propose that copy number analysis of the UBE3A gene should be considered in individuals whose clinical examination is strongly suggestive of AS, after more common mechanisms have been excluded. PMID: 21397058 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628346 Wed, 09 Mar 2011 00:00:00 +0100 4628346 http://www.medworm.com/index.php?rid=4628345&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21397059%26dopt%3DAbstract We report the case of a 26-month-old boy with mental retardation, facial dysmorphism, childhood feeding difficulties, short stature, bilateral cryptorchidism, micropenis, and heart defect. Endocrinal evaluation revealed complete growth hormone deficiency (GHD) and gonadotropic deficiency, and pituitary magnetic resonance imaging showed partial pituitary stalk interruption syndrome (PSIS). A de novo 493 kb microdeletion on chromosome 17q21.31 was identified using array comparative genomic hybridization (array-CGH) analysis. This is the first report of PSIS in thephenotypical spectrum of 17q21.31 microdeletion syndrome, although other midline abnormalities have previously been described. Our report suggests that GHD should be investigated in patients with 17q21.31 microdeletion syndrome and ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4628345 Wed, 09 Mar 2011 00:00:00 +0100 4628345 http://www.medworm.com/index.php?rid=4566421&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21376145%26dopt%3DAbstract We report a patient with a clinical phenotype of severe infantile CS who has a paternally inherited 5 Mb deletion of 10q11.2 resulting in loss of one allele and a previously unreported frameshift mutation of ERCC6 on the maternal allele. PMID: 21376145 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566421 Tue, 01 Mar 2011 00:00:00 +0100 4566421 http://www.medworm.com/index.php?rid=4566422&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21362501%26dopt%3DAbstract Authors: Weichert J, Schröer A, Amari F, Siebert R, Caliebe A, Nagel I, Gillessen-Kaesbach G, Mohrmann I, Hellenbroich Y Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked recessive disorder encompassing pre- and postnatal overgrowth and a variety of additional anomalies including craniofacial dysmorphism, macrocephaly, congenital heart defects and genitourinary anomalies. There is little published information regarding the prenatal presentation of SGBS in pregnancy. In the present report we describe the antenatal features of an affected fetus from 12 gestational weeks onwards, subsequently diagnosed with SGBS by molecular testing positive for GPC3 gene mutation. PMID: 21362501 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566422 Sat, 26 Feb 2011 00:00:00 +0100 4566422 http://www.medworm.com/index.php?rid=4566423&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21356335%26dopt%3DAbstract CONCLUSIONS: The presently proposed classification was found to be reliable and easy to use for patients with vascular malformations with growth disturbances. We invite both clinicians and researchers to comment on the classification, in order to improve it further. This way we may obtain our final aim of an internationally accepted classification of patients, which should facilitate both clinical treatment and care of, as well as research into the molecular background of entities combining vascular malformation and deregulated growth. PMID: 21356335 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566423 Fri, 25 Feb 2011 00:00:00 +0100 4566423 http://www.medworm.com/index.php?rid=4566426&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354344%26dopt%3DAbstract Authors: Gathwala G, Dalal P, Dalal JS, Choudhry O The association of Down's syndrome with aplastic anemia is extremely rare with only six such cases reported in world literature. Herein, we report a child of Down's syndrome with pancytopenia and hypocellular marrow. There was associated hypothyroidism and the pancytopenia resolved with thyroxine treatment. The child made uneventful recovery. PMID: 21354344 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566426 Thu, 24 Feb 2011 00:00:00 +0100 4566426 http://www.medworm.com/index.php?rid=4566425&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354345%26dopt%3DAbstract We report on an apparently normal 5 month-old boy with a X;Y complex rearrangement identified first on prenatal diagnosis and found on array-CGH to have a 7,6 Mb duplication of Xp22.3 chromosome and a deletion of Yq chromosome, distal to the AZFa locus. Karyotype analysis on amniotic fluid cell cultures revealed a de novo homogenous chromosome marker that we interpreted as an isochromosome Yp. FISH analysis using SRY probe revealed only one signal on the derivative Y chromosome. The final karyotype was interpreted as 46,X,der(Y)t(X;Y)(p22.31;q11.22). Translocation Xp22;Yq11 in male are very rare event and only 4 cases have been published, all showing mental retardation and malformations. Herein we discussed some possible explanation for this apparent phenotypic variability. PMID: 21354... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566425 Thu, 24 Feb 2011 00:00:00 +0100 4566425 http://www.medworm.com/index.php?rid=4566424&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354346%26dopt%3DAbstract We report on a 9-month old boy carrying a 21 Mb de novo 13q interstitial deletion. The imbalance was detected by chromosomal analysis and investigated by Fluorescence In Situ Hybridization (FISH) and Comparative Genomic Hybridization (array-CGH) using two different platforms: a BAC microarray with 516 kb resolution (Cytochip) and a 15 kb resolution oligonucleotide microarray (Agilent 244K). The deletion has been estimated to span 21.46 Mb on chromosomal bands 13q22.2 - 13q32.1. The patient has mild/moderate psychomotor retardation, growth hormone insufficiency, hypertelorism, short neck, micrognathia, hypotonia, dysplastic ears and other dysmorphic features. Further investigation revealed that the abnormality is de novo and causative of the patient's phenotype. The described patient is uni... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4566424 Thu, 24 Feb 2011 00:00:00 +0100 4566424 http://www.medworm.com/index.php?rid=4512241&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333764%26dopt%3DAbstract Authors: Lo-Castro A, El-Malhany N, Galasso C, Verrotti A, Nardone AM, Postorivo D, Palmieri C, Curatolo P Ring chromosome 18 [r(18)] is a disorder in which one or both ends of chromosome 18 are lost and joined forming a ring-shaped figures. R(18) patients can therefore show features of 18q-, 18p- syndrome or a combination of both, depending on the size of the 18p and 18q deleted regions. The phenotype of the r(18) is characterized by developmental delay/mental retardation, typical facial dysmorphisms, major abnormalities and immunological problems. Here we report a case of de novo mosaic r(18) with a characterization by array based comparative genomic hybridization analysis, and discuss the phenotypic correlation in r(18) also through a comparison with previously described cases of th... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512241 Wed, 16 Feb 2011 00:00:00 +0100 4512241 http://www.medworm.com/index.php?rid=4512240&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333765%26dopt%3DAbstract Authors: Busche A, Graul-Neumann LM, Zweier C, Rauch A, Klopocki E, Horn D Saethre-Chotzen syndrome due to TWIST1 mutations is characterized by coronal synostosis, facial dysmorphism and additional variable anomalies. Small deletions comprising the whole TWIST1 account for a small proportion of patients with Saethre-Chotzen syndrome. Here we describe 3 patients with facial dysmorphism, marked microcephaly, short stature (2/3 patients), and overlapping 7p21 microdeletions. Molecular karyotyping identified small deletions of chromosome 7p21 including TWIST1 with a size of 526kb, 9.2 Mb, and 11.7 Mb, respectively. The clinical manifestations of these patients do not resemble the typical phenotype of Saethre-Chotzen syndrome. In the two patients with larger microdeletions, severe mental re... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512240 Wed, 16 Feb 2011 00:00:00 +0100 4512240 http://www.medworm.com/index.php?rid=4512239&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333766%26dopt%3DAbstract We report a family with facial dysmorphism somewhat reminiscent of Robinow syndrome (flat face, very short, upturned nose, very long and unusually wide philtrum, and flattened maxillary arch), observed in 3 generations. Four sibs in the second generations had large omphaloceles. One child had ectrodactyly. Genomic rearrangements, and WNT5A or ROR2 mutations were excluded in this family. At this point, we feel reasonable to consider this family as expressing a "new" syndrome related but different from Robinow syndrome, associating facial dysmorphism and abdominal wall defect, and compatible with dominant inheritance with variable expressivity, although recessively inherited omphalocele occurring in a family showing independently some dominant craniofacial peculiarities cannot be ruled out. ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512239 Wed, 16 Feb 2011 00:00:00 +0100 4512239 http://www.medworm.com/index.php?rid=4512244&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21316495%26dopt%3DAbstract This report demonstrates the worth of advanced molecular (cyto)genetic techniques in characterizing sSMC, their utility in genotype-phenotype correlation and risk of clinical presentation. PMID: 21316495 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512244 Thu, 10 Feb 2011 00:00:00 +0100 4512244 http://www.medworm.com/index.php?rid=4512248&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315189%26dopt%3DAbstract We report a three-year-old boy with the 16p13.11 microdeletion syndrome, identified on arrayCGH, and describe his clinical phenotype, thereby adding to the existing literature on this newly-described microdeletion syndrome. We discuss the function and potential relevance of the genes in this region with regards to the features described in this condition. PMID: 21315189 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512248 Tue, 08 Feb 2011 00:00:00 +0100 4512248 http://www.medworm.com/index.php?rid=4512247&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315190%26dopt%3DAbstract Authors: Rejeb I, Ben Jemaa L, Abaied L, Kraoua L, Saillour Y, Maazoul F, Chelly J, Chaabouni H Mental retardation (MR) is the most frequent cause of serious handicap in children and young adults. Despite recent progress, in most cases the molecular defects underlying this disorder remain unknown. Linkage studies followed by mutational analysis of known X-chromosomal genes related to mental retardation (MRX genes) localized within defined genetic intervals represent a rational strategy to identify a genetic cause of the disorder. Here, we report a Tunisian family including 3 males with severe to mild mental retardation, short stature, lean body and microcephaly; we mapped the disease to a unique interval encompassing Xp21.1-Xq21.33 (with a maximum LOD score of 0.90). Subsequent mutatio... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512247 Tue, 08 Feb 2011 00:00:00 +0100 4512247 http://www.medworm.com/index.php?rid=4512246&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315191%26dopt%3DAbstract Authors: Agochukwu NB, Pineda-Alvarez DE, Keaton AA, Warren-Mora N, Raam MS, Kamat A, Chandrasekharappa SC, Solomon BD VACTERL association, a relatively common condition with an incidence of approximately 1 in 20,000 - 35,000 births, is a non-random association of birth defects that includes vertebral defects (V), anal atresia (A), cardiac defects (C), tracheo-esophageal fistula (TE), renal anomalies (R) and limb malformations (L). Although the etiology is unknown in the majority of patients, there is evidence that it is causally heterogeneous. Several studies have shown evidence for inheritance in VACTERL, implying a role for genetic loci. Recently, patients with component features of VACTERL and a lethal developmental pulmonary disorder, alveolar capillary dysplasia with misalignment... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512246 Tue, 08 Feb 2011 00:00:00 +0100 4512246 http://www.medworm.com/index.php?rid=4512245&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315192%26dopt%3DAbstract Authors: Salomon J, Espinosa-Parrilla Y, Goulet O, Al-Qabandi W, Guigue P, Canioni D, Bruneau J, Alzahrani F, Almuhsen S, Cerf-Bensussan N, Jeanpierre M, Brousse N, Lyonnet S, Munnich A, Smahi A Mutations of the EPCAM gene have been recently identified in Congenital Tufting Enteropathy (CTE), a severe autosomal recessive gastrointestinal insufficiency of childhood requiring parenteral nutrition and occasionally intestinal transplantation. Studying seven multiplex consanguineous families from the Arabic peninsula (Kuwait and Qatar) we found that most patients were homozygote for a c.498insC mutation in exon 5. The others carried a novel mutation IVS4-2A→G. Both mutations were predicted to truncate the C-terminal domain necessary to anchorage of EPCAM at the intercellular membrane. Con... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4512245 Tue, 08 Feb 2011 00:00:00 +0100 4512245 http://www.medworm.com/index.php?rid=4454673&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21276880%26dopt%3DAbstract Authors: Faguer S, De Sandre-Giovannoli A, Hemery M, Lévy N, Lamant L, Arveiler B, Rooryck C, Prouheze C, Vigouroux A, Chauveau D, Calvas P, Chassaing N PMID: 21276880 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4454673 Wed, 26 Jan 2011 00:00:00 +0100 4454673 http://www.medworm.com/index.php?rid=4454672&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21276881%26dopt%3DAbstract Authors: Salazar M, Consoli F, Villegas V, Caicedo V, Maddaloni V, Daniele P, Caianiello G, Pachón S, Nuñez F, Limongelli G, Pacileo G, Marino B, Bernal JE, De Luca A, Dallapiccola B High prevalence of somatic mutations in the cardiac transcription factor genes NKX2.5 and GATA4 have been reported in the affected cardiovascular tissue of patients with isolated cardiac septal defects, suggesting a role of somatic mutations in the pathogenesis of these congenital heart defects (CHDs). However, all somatic mutations have been identified in DNA extracted from an archive of formalin-fixed cardiac tissues. In the present study, to address the hypothesis that somatic mutations are important in isolated CHDs, we analyzed the GATA4 and NKX2.5 genes in the fresh-frozen pathologic cardiac tissue... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4454672 Wed, 26 Jan 2011 00:00:00 +0100 4454672 http://www.medworm.com/index.php?rid=4454674&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21262397%26dopt%3DAbstract We describe 2 unrelated patients presenting with multiple circumferential skin creases, growth retardation, developmental delay, a typical facial appearance and cleft palate. In literature, 6 patients with an almost identical clinical phenotype have been described. This well recognizable syndrome should be distinguished from the "Michelin Tire Baby" syndrome and we therefore propose the term "circumferential skin creases Kunze type". PMID: 21262397 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4454674 Fri, 21 Jan 2011 00:00:00 +0100 4454674 http://www.medworm.com/index.php?rid=4388708&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21252004%26dopt%3DAbstract Authors: Belligni EF, Dokal I, Hennekam RC Naegeli(-Franceschetti-Jodasson) syndrome and Dermatopathia Pigmentosa Reticularis are allelic disorders, both characterized by a congenital generalized reticulate hyperpigmentation, palmoplantar hyperkeratosis and other ectodermal symptoms. The disorders differ in their primary pigmentation localization and hair and dental manifestations. They resemble Dyskeratosis Congenita and Poikiloderma Clericuzio type in many of the skin changes, but especially the presence of leukoplakia and bone marrow disfunctioning in the first, and of teleangectasias, generalized hyperkeratosis of palms and soles, and nail pachyonychia in the latter are distinguishing features. Here we present two unrelated patients who have prenatal and postnatal growth retardatio... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388708 Mon, 17 Jan 2011 00:00:00 +0100 4388708 http://www.medworm.com/index.php?rid=4388707&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21252005%26dopt%3DAbstract Authors: Boonen SE Diploid/triploid mosaicism is a well-known malformation syndrome sharing some clinical features with different imprinting syndromes. The phenotype in our patient overlaps with some of the phenotypic features seen in Silver-Russell syndrome, Prader-Willi syndrome and maternal uniparental disomy of chromosome 14, which all can be caused by maternal over expression of imprinted genes. Interestingly, the extra chromosome set identified in our patient is of maternal origin. Most patients with diploid/triploid mosaicism have a normal blood karyotype and the diagnosis can only be established after analysis of other tissues such as skin fibroblasts. To date, less than 35 patients have been described in the literature. Here we present the first Danish diploid/triploid mosaici... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388707 Mon, 17 Jan 2011 00:00:00 +0100 4388707 http://www.medworm.com/index.php?rid=4388709&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21215339%26dopt%3DAbstract We report an unusual chromosome 22q11 deletion associated with an apparent complementary ring chromosome in a phenotypically normal woman with a family medical history of 22q11 deletion. Using peripheral blood samples, conventional karyotyping, Fluorescence In Situ Hybridization (FISH) analysis on metaphase spreads and oligo array-based comparative genomic hybridisation (oligo array-CGH) were performed. After conventional cytogenetic examination, the chromosome formula was as follows: 47,XX,+r(?)[16]/46,XX[6]. The FISH analysis revealed that this patient had a rearranged chromosome 22 with decreased centromeric fluorescence intensity and deletion of the 22q11.2 locus. She also had a supernumerary ring chromosome composed of an alphasatellite centromere of 22 origin and 22q11.2 locus. The o... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388709 Tue, 04 Jan 2011 00:00:00 +0100 4388709 http://www.medworm.com/index.php?rid=4388711&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21211576%26dopt%3DAbstract Authors: Chiara M, Giovanna P, Alba P, Traversa M, Fabio B, Sergio B To date, more than 100 cases with a deletion of chromosome 2q have been identified, although studies reporting small interstitial deletions involving the 2q24.2-q24.3 region are still rare. Here, we have described the genotype and the phenotype of a boy with a 5.3 Mb de novo deletion in this region, identified by SNP array analysis. The selected region included 20 genes, of which 4 are prominently expressed in the brain. Their combined haplo-insufficiency could explain the main clinical features of this patient which included mental retardation, severe hypotonia, joint laxity and mild dysmorphic traits. PMID: 21211576 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388711 Mon, 03 Jan 2011 00:00:00 +0100 4388711 http://www.medworm.com/index.php?rid=4388710&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21211577%26dopt%3DAbstract Authors: Oexle K, Hempel M, Jauch A, Meitinger T, Rivera-Brugués N, Stengel-Rutkowski S, Strom T In a male patient with developmental delay, autistic behaviour, obesity, lymphedema, hypertension, macrocephaly, and facial features of chromosome 5p duplication (trisomy 5p) a 3.7 Mb de novo tandem microduplication of 5p13.1-13.2 (rs4703415-rs261752, i.e., chr5:35.62-39.36Mb) was identified. This observation contributes to the characterization and dissection of the 5p13 duplication syndrome. The possible role of increased NIPBL gene dosage is discussed. PMID: 21211577 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388710 Mon, 03 Jan 2011 00:00:00 +0100 4388710 http://www.medworm.com/index.php?rid=4388712&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21199695%26dopt%3DAbstract We present one three generation family in which the proband has absence of the right ulna and third, fourth and fifth rays in her right hand. Her mother and maternal grandmother have more subtle anomalies while all have a similar facial appearance with a broad nasal tip, a broad jaw, a prominent chin and a tongue frenulum. They have a single base pair insertion (c. 992dup) in TBX3. We compare faces from the handful of published UMS patients which include photographs, this family and four other cases with TBX3 mutations. All have similarities in appearance which we suggest could alert clinicians to the possibility of a TBX3 mutation if individuals present with more subtle features of UMS such as postaxial polydactyly, isolated 5(th) finger anomalies, delayed puberty in males, breast hypopla... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388712 Fri, 31 Dec 2010 00:00:00 +0100 4388712 http://www.medworm.com/index.php?rid=4388713&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21195811%26dopt%3DAbstract We describe here a 13-year-old girl with a novel microduplication of the MDS critical region, involving the PAFAH1B1 and YWHAE genes. She presented with moderate psychomotor retardation, speech delay, behavioural problems, and bilateral cleft lip and palate, a previously unreported manifestation. Initially diagnosed as having an apparently simple terminal Xq26 deletion on standard cytogenetic analysis, she was found to have an associated terminal 4.2 Mb 17p13.3 submicroscopic duplication, identified by subtelomere FISH analysis, further characterized by high-resolution array CGH, resulting from an unbalanced X;17 translocation. Phenotypic comparison with the 5 other patients previously described, revealed common phenotypic features, such as hypotonia, mild to moderate developmental delay/m... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388713 Thu, 30 Dec 2010 00:00:00 +0100 4388713 http://www.medworm.com/index.php?rid=4388714&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21194575%26dopt%3DAbstract Authors: de Wit MC, Tiddens HA, de Coo IF, Mancini GM Recently in this journal, Masurel-Paulet et al. reported the association between pulmonary disease and a mutation in X-linked FLNA in a male patient. We confirm this association in a female patient, showing that this complication is not sex-specific. Our patient has a FLNA missense mutation (c.220G > A) and presented with cerebral periventricular nodular heterotopia, cardiovascular abnormalities, and pulmonary disease consisting of lobar emphysema of the right middle pulmonary lobe with severe malacia of the right sided bronchus intermedius. Surgical resection of the right middle lobe was necessary and she had long-term oxygen dependency. Symptoms improved with age. PMID: 21194575 [PubMed - as supplied by publisher] (Sourc... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4388714 Wed, 29 Dec 2010 00:00:00 +0100 4388714 http://www.medworm.com/index.php?rid=4298849&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21187175%26dopt%3DAbstract We report an 18 year old male diagnosed with a teratoid/rhabdoid tumour and distal 22q11.2 deletion syndrome. The distal 22q11.2 deletion encompasses the INI1/SMARCB1 tumour suppressor gene. Biallelic inactivation of this gene is characteristic of atypical teratoid/rhabdoid tumour [7.8]. PMID: 21187175 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298849 Fri, 24 Dec 2010 00:00:00 +0100 4298849 http://www.medworm.com/index.php?rid=4298848&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21187176%26dopt%3DAbstract We report seven new patients belonging to six families, age 9 to 24 years old, with a 350 kb 15q11.2 deletion of the four highly conserved genes (TUBGCP5, NIPA1, NIPA2 and CYFIP1) earlier reported. All our patients had some degree of learning difficulties, delayed development and/or behavioural problems. Common dysmorphic features and congenital malformations were not characteristics of our patients. The deletion was inherited from a mildly affected parent in all cases tested (5/6 families available for testing both parents). These seven new cases confirm some of the phenotype earlier reported to be associated with 15q11.2 deletion, and help to further delineate the phenotype associated with 15q11.2 deletion. PMID: 21187176 [PubMed - as supplied by publisher] (Source: European Journal ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298848 Fri, 24 Dec 2010 00:00:00 +0100 4298848 http://www.medworm.com/index.php?rid=4298851&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21172461%26dopt%3DAbstract Authors: Nakamura E, Makita Y, Okamoto T, Nagaya K, Hayashi T, Sugimoto M, Manabe H, Taketazu G, Kajino H, Fujieda K All patients with terminal deletion of chromosome 15q have been reported to show intrauterine growth retardation, postnatal growth retardation, abnormal facial appearance and developmental delay. Haploinsufficiency of IGF1R was considered to be responsible for these symptoms. However, it is difficult to explain other symptoms seen in some of the patients, such as congenital heart defects by the absence of IGF1R alone. Here, we reported a patient with congenital heart defects and a 5.78Mb terminal deletion of chromosome 15q detected by array-CGH. Among the patients reported to share congenital heart defects and terminal deletion of chromosome 15q, our patient had the smal... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298851 Fri, 17 Dec 2010 00:00:00 +0100 4298851 http://www.medworm.com/index.php?rid=4298850&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21172462%26dopt%3DAbstract In this study we used single nucleotide polymorphism (SNP) array-based, whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease, limb girdle muscular dystrophy (LGMD). In a consanguineous family, both affected siblings showed homozygous blocks on chromosome 15 corresponding to the LGMD2A locus. Direct sequencing of CAPN3, encoding calpain-3, identified a homozygous deletion c.483delG (p.I162SfsX17). In a sporadic LGMD patient complete absence of caveolin-3 on Western blot was observed. However, a mutation in CAV3 could not be detected. Homozygosity mapping revealed a large homozygous block at the LGMD2I locus, and direct sequencing of FKRP encoding fukutin-related-protein detected the common homozygous c.826 C>A (p.Leu276Il... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298850 Fri, 17 Dec 2010 00:00:00 +0100 4298850 http://www.medworm.com/index.php?rid=4298853&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21167328%26dopt%3DAbstract We report a boy with asymmetric crying facies and bilateral absence of the 5(th) ray of the feet. In addition, craniofacial computed tomography showed a solitary median maxillary central incisor in combination with a narrow apertura piriformis. To our knowledge this intriguing combination of congenital abnormalities has not been described before. PMID: 21167328 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298853 Tue, 14 Dec 2010 00:00:00 +0100 4298853 http://www.medworm.com/index.php?rid=4298852&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21167329%26dopt%3DAbstract We report on the clinical, cytogenetic and molecular findings of a 5-year-old patient with a de novo interstitial deletion from 3q25.1 to 3q25.32. Clinical features include relative microcephaly, developmental delay and facial dysmorphism with a coarse face, ptosis, synophrys, epicanthic folds, broad nasal bridge, long philtrum, large mouth with full lips, dysplastic and low set ears. Revealed by conventional banding techniques, the deleted region of 8.9 Mb was confirmed by fluorescent in situ hybridization (FISH) analyses and array comparative genomic hydridization (array-CGH). To our knowledge, this is the smallest interstitial deletion reported in the 3q25 region. The phenotype of our patient is compared with the 10 previously reported cases implicating the 3q25 region. PMID: 211673... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4298852 Tue, 14 Dec 2010 00:00:00 +0100 4298852 http://www.medworm.com/index.php?rid=4266576&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21147279%26dopt%3DAbstract Authors: Hennekam RC There is increasing attention by policy makers and health authorities for rare disorders (by definition prevalence <1:2000). The attention for ultra-rare disorders (suggested prevalence one-thousandth of rare disorders, so <1:2,000,000) is very limited however. Here some aspects of organizing adequate care for individuals with ultra-rare disorders in a European setting are discussed. Individual ultra-rare disorders are by definition very uncommon but it can be calculated that as a group they form a considerable part of the total group of persons with rare disorders in the European Community (EC). Diagnostics and regular care for individuals with rare disorders is being arranged in national centres of expertise, but due to small individual numbers this is not ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266576 Fri, 10 Dec 2010 00:00:00 +0100 4266576 http://www.medworm.com/index.php?rid=4266581&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145991%26dopt%3DAbstract Authors: Kosztolányi G, Brecevic L, Bajnòczky K, Schinzel A, Riegel M Additional small ring chromosome 1 is describedwith increasing rate of mosaicism in three generations. Ten years after the first examination, the mosaic rates in the patients were strikingly similar. An increase in the expression of phenotypic anomalies was also observed in the successive generations. FISH examinations following microdissection revealed signals which were positive for 1p13 and 1q21 indicating that the ring contained euchromatic segments on both ends. Additionally, array-CGH whole-genome analysis showed a single copy gain corresponding to band 1p12 to band 1q21-1 of chromosome 1 in the patients. The presence of euchromatic material fromchromosome 1 in the ring suggests that the relationship between ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266581 Wed, 08 Dec 2010 00:00:00 +0100 4266581 http://www.medworm.com/index.php?rid=4266580&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145992%26dopt%3DAbstract In this study, we sequenced the entire coding region of the MLC1 gene in 13 patients and detected five novel nucleotide variations in six of them. Two of the novel variations created a missense amino acid change and the other three were located in the introns and were putative splice mutations. One novel missense variation was observed in two unrelated patients from the central Black Sea region, and the data suggested a founder haplotype for this novel variation. Similarly, three unrelated patients with the previously reported p.Thr118Arg mutation shared a common haplotype. These data suggest an Anatolian origin for these two mutations. As in the previous reports, it is not possible to correlate the clinical phenotype of the patients with the mutation spectra. PMID: 21145992 [PubMed - ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266580 Wed, 08 Dec 2010 00:00:00 +0100 4266580 http://www.medworm.com/index.php?rid=4266579&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145993%26dopt%3DAbstract Authors: Culic V, Betz RC, Refke M, Fumic K, Pavelic J In the present study we report the clinical features and the molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in a young girl from Croatia with Richner-Hanhart syndrome, mainly suffering from photophobia, hyperkeratosis of the palmes and soles and slight neurological abnormalities. Sequencing analysis of the TAT gene revealed a novel homozygous missense mutation c.1250G>A (p.R417Q) in exon 12, and herewith confirmed the clinical diagnosis. Showing the first symptoms in babyhood, at the age of 8 years it was for the first time clinically diagnosed that the patient suffers from tyrosinemia type II and a therapy with tyrosine and phenylalanine reduced diet has been started successfully. All symptoms disap... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266579 Wed, 08 Dec 2010 00:00:00 +0100 4266579 http://www.medworm.com/index.php?rid=4266578&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145994%26dopt%3DAbstract Authors: Bouquillon S, Andrieux JR, Landais E, Duban-Bedu B, Boidein F, Lenne B, Vallée L, Leal T, Doco-Fenzy M, Delobel B Interstitial 18q deletions encompassing band 18q12.3 define the del(18)(q12.2q21.1) syndrome. Usual manifestations are mild dysmorphic features, mental retardation, behaviour abnormalities and lack of serious malformation. Seizures have also been found. Recently, more specifically, impairment of expressive language has been reported. PMID: 21145994 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266578 Wed, 08 Dec 2010 00:00:00 +0100 4266578 http://www.medworm.com/index.php?rid=4266577&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21145995%26dopt%3DAbstract We report an 11-year-old girl with 1p36 deletion and the classical dysmorphological features. In late infancy, she developed an uncontrolled voracious appetite, overweight, truncal obesity and elevated serum transaminases. Liver biopsy disclosed severe steatosis. The hepatocytes contained accumulation of lipofuscins. Lipolysosomes were abnormally numerous and extremely enlarged. These features have not been previously reported in 1p36 deletion. Oligonucleotide-based microarray analysis showed a subtelomeric 2.2 Mb deletion at 1p36.33p36.32. This suggests that this chromosome segment is a critical region for obesity and hyperphagia. The accumulation in the liver with abnormal ultrastructure may be an additional feature of this form of syndromal obesity. 1p36 deletion syndrome should be cons... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266577 Wed, 08 Dec 2010 00:00:00 +0100 4266577 http://www.medworm.com/index.php?rid=4266583&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21144913%26dopt%3DAbstract Authors: Abdelmoity AT, Hall JJ, Bittel DC, Yu S We identified a novel 1.39 Mb interstitial deletion of chromosome 12p13.33 in an 8 year old Caucasian female propositus and her affected father and brother using microarray-based comparative genomic hybridization (aCGH). They share a history of developmental delay and staring episodes. The deleted region contains eight annotated genes (ERC1, FBXL14, WNT5B, ADIPOR2, CACNA2D4, LRTM2, DCP1B, and CACNA1C). Hemizygous deletions of ERC1, FBXL14, or WNT5B genes may be involved in the development of neurological disorders in these individuals. Furthermore, the centromeric breakpoint of the 1.39 Mb deleted region is the same as the centromeric breakpoint of a 2.3 Mb terminal deletion of 12p13.33 reported recently, indicating the presence of an un... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266583 Mon, 06 Dec 2010 00:00:00 +0100 4266583 http://www.medworm.com/index.php?rid=4266582&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21144914%26dopt%3DAbstract We describe 2 children with dysmorphic features, and severe developmental delay presenting with overlapping unbalanced translocations of 9q34.3 and 16p13. Patient #1: A 4 year old African American female with normal karyotype with a pericentric inversion on one chromosome 9 known to be a benign variant. Low resolution array CGH revealed a single BAC clone loss at 9q34.3 and a single BAC clone gain at 16p13.3, confirmed by FISH. Whole genome SNP array analysis refined these findings, identifying a terminal 1.28 Mb deletion (138,879,862-140,164,310 bp) of 9q34.3 and a terminal 1.62 Mb duplication (45,320-1,621,753) of 16p13.3. Subtelomeric FISH showed an unbalanced cryptic translocation involving the inverted chromosome 9 and chromosome 16. FISH of the father showed a balanced t(9;16)(q34.3;... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4266582 Mon, 06 Dec 2010 00:00:00 +0100 4266582 http://www.medworm.com/index.php?rid=4243441&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21115145%26dopt%3DAbstract We report the case of a female patient exhibiting multiple congenital malformations including diaphragmatic hernia and heart defect. Cytogenetic studies (including karyotype, FISH and array-CGH) showed a de novo terminal deletion (6.9-Mb) on chromosome 15 in association with a recombinant X chromosome bearing a 9-Mb Xp duplication and a 46-Mb Xq deletion distal to XIST. The recombinant X chromosome was caused by a maternal inv(X)(p22.31q22.3). The X chromosome inactivation pattern was skewed in the patient suggesting a possible inactivation of the recombinant X chromosome. Considering these results, the phenotype was linked to the de novo terminal 15q deletion. These results strengthen the assumption that array-CGH should be applied to each fetus/newborn with multiple congenital malformati... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4243441 Fri, 26 Nov 2010 00:00:00 +0100 4243441 http://www.medworm.com/index.php?rid=4211754&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112420%26dopt%3DAbstract In this study whole-genome SNP arrays were used to investigate genomic rearrangements in 77 Estonian families with idiopathic mental retardation. In addition to this family-based approach, phenotype and genotype data from a cohort of 1000 individuals in the general population were used for accurate interpretation of aberrations found in mental retardation patients. Relevant structural aberrations were detected in 18 of the families analyzed (23%). Fifteen of those were in genomic regions where clinical significance has previously been established. In 3 families, 4 novel aberrations associated with intellectual disability were detected in chromosome regions 2p25.1-p24.3, 3p12.1-p11.2, 7p21.2-p21.1 and Xq28. Carriers of imbalances in 15q13.3, 16p11.2 and Xp22.31 were identified among referen... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4211754 Thu, 25 Nov 2010 00:00:00 +0100 4211754 http://www.medworm.com/index.php?rid=4211758&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094704%26dopt%3DAbstract Authors: Zhang X, Zhu D, Lan H, Yu L, Peng W, Mei Y, Feng Z Langerhans'cell histiocytosis (LCH) is a rare disease of unkown cause and is characterized by clonal proliferation of Langerhans cells. Here, we describe the case of a 22-month-old boy with LCH associated with X-linked lymphoproliferative disease (XLP). Sequence analysis of SH2D1A for mutations that cause T-cell dysfunction revealed a CT substitution at nucleotide 462. This is the first case that hints at an association between XLP and LCH. PMID: 21094704 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4211758 Fri, 19 Nov 2010 00:00:00 +0100 4211758 http://www.medworm.com/index.php?rid=4211757&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094705%26dopt%3DAbstract We present two further cases, diagnosed after termination of pregnancy at 24 weeks' gestation in one case and straight after birth in the other, both very similar to the previously reported ones, and broaden the clinical spectrum of this entity. To our knowledge, no molecular mechanism has been identified in Crane-Heise syndrome so far. PMID: 21094705 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4211757 Fri, 19 Nov 2010 00:00:00 +0100 4211757 http://www.medworm.com/index.php?rid=4211756&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094706%26dopt%3DAbstract We report here the clinical and molecular characterization of a new series of 14 French patients with this microdeletion syndrome. The most frequent clinical features were hypotonia, developmental delay and facial dysmorphism, but scaphocephaly, prenatal ischemic infarction and perception deafness were also described. Genotyping of the parents showed that the parent from which the abnormality was inherited carried the H2 inversion polymorphism, confirming that the H2 allele is necessary, but not sufficient to generate the 17q21.31 microdeletion. Previously reported molecular analyses of patients with 17q21.31 microdeletion syndrome defined a 493 kb genomic fragment that was deleted in most patients after taking into account frequent copy number variations in normal controls, but the delete... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4211756 Fri, 19 Nov 2010 00:00:00 +0100 4211756 http://www.medworm.com/index.php?rid=4211755&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21094707%26dopt%3DAbstract We describe a patient with a pattern of malformations reminiscent of CHARGE syndrome: choanal atresia, facial dysmorphism (micrognathia, hypertelorism, epicanthic folds, and depressed, broad nasal bridge), cardiovascular malformations, cryptorchidism, and developmental delay. He had duplication 8q and deletion 4q derived from paternal translocation t(4;8)(q34;q22.1). CHD7 mutation or deletion was excluded. The present report to the best of our knowledge is the only one describing an unbalanced translocation t(4;8) and CHARGE-like phenotype. PMID: 21094707 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4211755 Fri, 19 Nov 2010 00:00:00 +0100 4211755 http://www.medworm.com/index.php?rid=4180524&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21078420%26dopt%3DAbstract Authors: Reshmi SC, Miller JL, Deplewski D, Close C, Henderson LJ, Littlejohn E, Schwartz S, Waggoner DJ Abnormalities involving sex chromosomes account for approximately 0.5% of live births. The phenotypes of individuals with mosaic cell lines having structural aberrations of the X and Y chromosomes are variable and hard to accurately predict. Phenotypes associated with sex chromosome mosaicism range from Turner syndrome to males with infertility, and often present with ambiguous genitalia. Previous studies of individuals with an 45,X/46,X,idic(Y)(p11) karyotype suggest that the presence of both cell lines should result from an intermediate, 46,XY cell line. Here we report a 2.5 year old female with phenotypic features of Turner syndrome with an isodicentric Y chromosome and a cell li... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4180524 Fri, 12 Nov 2010 00:00:00 +0100 4180524 http://www.medworm.com/index.php?rid=4163645&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056703%26dopt%3DAbstract We present our validation data on the detection of chromosome mosaicism by oligonucleotide array CGH, and the cases detected in a cohort of 3,042 clinical referrals. Using an artificial mosaicism series, we found that oligonucleotide array CGH using specific analysis parameters could accurately measure levels of mosaicism down to 10% and that the degree of mosaicism could be predicted from fluorescence ratios. We detected 12 cases of mosaicism in our clinical cohort, in 9 of which there was no previous indication of mosaicism. In two cases, G-banded chromosome analysis had been carried out previously, and had failed to detect the abnormal cell line. Three cases had mosaicism for the X chromosome and 9 involved autosomes, of which 4 were mosaic for whole chromosome trisomies, one for whole ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4163645 Thu, 04 Nov 2010 00:00:00 +0100 4163645 http://www.medworm.com/index.php?rid=4163644&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21056704%26dopt%3DAbstract Authors: Paskulin GA, Riegel M, Machado Rosa RF, Graziadio C, Gazzola Zen PR Carriers of paracentric inversions (PAIs) are usually asymptomatic. However, such inversions may lead to formation of recombinant gametes and then to an abnormal gestation. Here we report a girl with a 7q31.32→q33 deletion secondary to a maternal PAI of chromosome 7. This finding was confirmed through FISH and whole-genome array-CGH analyses. The deficiency of the chromosome 7 observed in our patient was never described before and we did not find any known gene localized within the deficient segment that could be related to her findings of hypoplastic iliac bones, hypoplastic labia minora and postaxial polydactyly. This case highlights the fact that rare viable recombinants can be developed from PAIs, an iss... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4163644 Thu, 04 Nov 2010 00:00:00 +0100 4163644 http://www.medworm.com/index.php?rid=4134598&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21044704%26dopt%3DAbstract Authors: Kulseth MA, Lyle R, Rødningen OK, Sorte H, Prescott T It can be difficult to assess the clinical significance of novel genomic sequence variants which may potentially alter mRNA splicing. Segregation analysis is not helpful in isolated cases or small families. Bioinformatic tools can provide additional information, but direct analysis of mRNA from an appropriate tissue remains the preferred approach for analyzing the effect of a sequence variant on splicing. However, hundreds of disease-associated and developmental genes, including the Sonic Hedgehog homolog (SHH) gene, are not expressed in blood or fibroblasts postnatally. We identified a de novo nucleotide change, c.301-19G>A, in intron 1 of SHH in a four year old boy with a microform of holoprosencephaly. In silico anal... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4134598 Sat, 30 Oct 2010 00:00:00 +0100 4134598 http://www.medworm.com/index.php?rid=4134597&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21044901%26dopt%3DAbstract We report 7 patients diagnosed in the neonatal period with hydrometrocolpos and polydactyly who carry mutations in various BBS genes (BBS6, BBS2, BBS10, BBS8 and BBS12), stressing the importance of wide BBS genotyping in patients with this clinical association for diagnosis, prognosis and genetic counselling. PMID: 21044901 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4134597 Thu, 28 Oct 2010 00:00:00 +0100 4134597 http://www.medworm.com/index.php?rid=4134599&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035572%26dopt%3DAbstract This report urges caution in interpreting SNPs in databases in the clinical genetics setting and calls for sequencing runs of homozygosity in healthy individuals as a promising approach to better annotate SNP databases. PMID: 21035572 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4134599 Wed, 27 Oct 2010 00:00:00 +0100 4134599 http://www.medworm.com/index.php?rid=4134600&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21034864%26dopt%3DAbstract Authors: Panichareon B, Taweechue K, Thongnoppakhun W, Aksornworanart M, Pithukpakorn M, Yenchitsomanus PT, Limwongse C, Limjindaporn T WD is an autosomal recessive disorder of copper transport resulting in excessive copper deposition in the liver and brain. It is caused by defects of ATP7B encoding a copper transporting P-type ATPase. To identify the mutations in ATP7B in Thai patients with WD, DHPLC analysis was applied to detect mutations and polymorphisms of the entire ATP7B gene in 19 Thai patients with WD. Mutations in ATP7B were identified in 14 of 19 patients: 2 homozygotes, 8 compound heterozygotes and 4 heterozygotes. Eighteen mutations distributed throughout the entire coding region of ATP7B gene including 11 missense, 3 nonsense, 1 splice-site, 1 deletion and 2 insertions. ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4134600 Tue, 26 Oct 2010 00:00:00 +0100 4134600 http://www.medworm.com/index.php?rid=4120968&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20974300%26dopt%3DAbstract This study has expanded the phenotypic spectrum of known HOXD13 polyalanine repeat mutations and provided more information about the polymorphic nature of the polyalanine repeat. In addition, new clinical manifestations have been added to the spectrum of possible synpolydactyly phenotypes. PMID: 20974300 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4120968 Fri, 22 Oct 2010 00:00:00 +0100 4120968 http://www.medworm.com/index.php?rid=4106544&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971220%26dopt%3DAbstract Authors: Aleem AA, Abu-Shahba N, Swistun D, Silhavy J, Bielas SL, Sattar S, Gleeson JG, Zaki M Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with this corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent c... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106544 Wed, 20 Oct 2010 23:00:00 +0100 4106544 http://www.medworm.com/index.php?rid=4106546&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970527%26dopt%3DAbstract In this study, we describe chimeric CYP21A1P/CYP21A2 genes detected in our patients with 21-hydroxylase deficiency (21OHD). Chimeric CYP21A1P/CYP21A2 genes were present in 171 out of 508 mutated CYP21A2 aleles (33.8%). We detected four types of chimeric CYP21A1P/CYP21A2 genes: three of them have been described previously as CH-1, CH-3, CH-4, and one type is novel. The novel chimeric gene, termed CH-7, was detected in 21.4% of the mutant alleles. Possible causes of CYP21A1P/CYP21A2 formation are associated with 1) high recombination rate in the MHC locus, 2) high recombination rate between highly homologous genes and pseudogenes in the CYP21 gene area, and 3) the existence of chi-like sequences and repetitive minisatellite consensus sequences in CYP21A2 and CYP21A1P which play a role in pro... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106546 Tue, 19 Oct 2010 23:00:00 +0100 4106546 http://www.medworm.com/index.php?rid=4106548&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20969981%26dopt%3DAbstract We describe a 6-year-old boy carrying a de novo 5 Mb interstitial deletion of chromosome 8p23.1 identified by means of oligonucleotide array comparative genomic hybridisation (array CGH), who showed the typical signs of 8p23.1 deletion syndrome, including congenital heart defects, microcephaly, psychomotor delay and behavioural problems. In order to estimate the role of suggested candidate genes, we compared the deletion of our patient with other previously reported and molecularly characterised deletions that have been re-evaluated on the basis of the current genetic map data. The inclusion of TNKS gene in the deletion interval without any phenotypical signs of Cornelia de Lange syndrome (CdLS) invalidates TNKS as a plausible candidate gene for the syndrome itself. PMID: 20969981 [Pub... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106548 Mon, 18 Oct 2010 23:00:00 +0100 4106548 http://www.medworm.com/index.php?rid=4106551&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20965291%26dopt%3DAbstract This study suggested the feasibility of a step by step screening of endometrial cancers to select patients at risk for Lynch syndrome and for whom a genetic test would be recommended. Authors suggest that either Amsterdam or Bethesda criteria should be systematically used prospectively in every newly diagnosed endometrial cancer and retrospectively using clinical data bases available on endometrial cancers. PMID: 20965291 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106551 Sun, 17 Oct 2010 23:00:00 +0100 4106551 http://www.medworm.com/index.php?rid=4106550&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20965292%26dopt%3DAbstract CONCLUSION: Rimonabant administration may be efficacious for weight loss in adults with PWS; unfortunately it is associated with an unacceptably high risk of psychiatric side effects. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition. PMID: 20965292 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106550 Sun, 17 Oct 2010 23:00:00 +0100 4106550 http://www.medworm.com/index.php?rid=4106549&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20965293%26dopt%3DAbstract CONCLUSIONS: Clinical assessment identifies less than 3/4 patients with a 22q11.2 deletion, whereas more than 1/4 remain undiagnosed if genetic tests are not performed on a routine basis. In this review, we found that clinical assessment is not suited for detecting individuals to be tested for 22q11.2 deletions. PMID: 20965293 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106549 Sun, 17 Oct 2010 23:00:00 +0100 4106549 http://www.medworm.com/index.php?rid=4106556&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20950717%26dopt%3DAbstract This report illustrates the power of databases such as DECIPHER and MRNET in assessing the pathogenicity of copy-number variations (CNVs). PMID: 20950717 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106556 Wed, 13 Oct 2010 23:00:00 +0100 4106556 http://www.medworm.com/index.php?rid=4106552&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951845%26dopt%3DAbstract Authors: Rosenfeld JA, Lacassie Y, El-Khechen D, Escobar LF, Reggin J, Heuer C, Chen E, Jenkins LS, Collins AT, Zinner S, Babcock M, Morrow B, Schultz RA, Torchia B, Ballif BC, Tsuchiya KD, Shaffer LG Microdeletions of 1q41q42 have recently been classified as a syndrome. Features include significant developmental delay and characteristic dysmorphic features as well as cleft palate, clubfeet, seizures, and short stature in some individuals, with a clinical diagnosis of Fryns syndrome in two individuals with congenital diaphragmatic hernia at the severe end of the spectrum. The gene DISP1, which is involved in sonic hedgehog signaling, has been proposed as a candidate for the the midline defects in this syndrome. We undertook a genotype-phenotype analysis of seven previously unreported i... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4106552 Wed, 13 Oct 2010 23:00:00 +0100 4106552 http://www.medworm.com/index.php?rid=4074952&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937419%26dopt%3DAbstract Authors: Medlej-Hashim M, Chouery E, Salem N, Delague V, Lefranc G, Loiselet J, Mégarbané A Familial Mediterranean fever (FMF) is an autoinflammatory autosomal recessive disease characterized by recurrent fever crises and serous inflammation. The MEFV gene responsible for the disease was identified on chromosome 16, and 5 of the mutations discovered so far in the gene are most frequently encountered in FMF patients: p.[M694V], p.[V726A], p.[M680I] and p.[M694I] in exon 10, and p.[E148Q] in exon 2. The present work describes multiple MEFV mutations and the corresponding haplotypes for 31 FMF patients as well as 32 «healthy» individuals of a large consanguineous Lebanese family. The DNAs were screened for MEFV mutations, and determination of the corresponding haplotypes was performed... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4074952 Thu, 07 Oct 2010 23:00:00 +0100 4074952 http://www.medworm.com/index.php?rid=4057563&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933618%26dopt%3DAbstract This report illustrates how knowledge of genes within a deleted interval facilitates optimal medical management, can explain observed phenotypes, and stimulates research questions. PMID: 20933618 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4057563 Tue, 05 Oct 2010 23:00:00 +0100 4057563 http://www.medworm.com/index.php?rid=4057562&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933619%26dopt%3DAbstract In conclusion, our results strongly suggest that the 3 bp deletion is a loss-of-function mutation of the maternal UBE3A allele that has caused Angelman syndrome in our patient. Our study may serve as a paradigm to determine the parental origin of a de novo mutation. PMID: 20933619 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4057562 Tue, 05 Oct 2010 23:00:00 +0100 4057562 http://www.medworm.com/index.php?rid=4057561&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933620%26dopt%3DAbstract We report a 35 year old male with a ring chromosome 12 originally diagnosed twenty years prior to presentation with an ischemic stroke. Array CGH analysis revealed a sub-microscopic microdeletion and microduplication within 12p13.3 and a microdeletion in 12q24.33. FISH analysis further revealed that the duplication was in an inverted orientation and included exons 35 to 52 of the dosage-sensitive Von Willebrand Factor (VWF) gene. Partial duplication of this gene, which has a role in the clotting cascade, suggests a potential mechanism for generating a pro-thrombotic state that may have contributed to a premature cerebrovascular event.Evidence of raised VWF antigen levels and VWF activity levels in the highest quartile provides support for this hypothesis. This case illustrates that when a ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4057561 Tue, 05 Oct 2010 23:00:00 +0100 4057561 http://www.medworm.com/index.php?rid=4057560&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933621%26dopt%3DAbstract We report a de novo 12q13.11 deletion of 1.3 Mb in an 10-year-old dysmorphic girl with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome consisting mainly of severe mental retardation, cleft palate, and high myopia. The deleted region encompasses 16 RefSeq genes. Among these, it is hypothesized that haploinsufficiency of AMIGO2 is potentially responsible for the mental retardation of this patient, and of COL2A1 for the cleft palate and high myopia. PMID: 20933621 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4057560 Tue, 05 Oct 2010 23:00:00 +0100 4057560 http://www.medworm.com/index.php?rid=4057564&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20932945%26dopt%3DAbstract Authors: Corona-Rivera JR, Romo-Huerta CO, López-Marure E, Ramos FJ, Estrada-Padilla SA, Zepeda-Romero LC The Yunis-Varón syndrome (YVS) represents a rare autosomal recessive syndrome of easy recognition characterized by cleidocraneal dysplasia, absence of thumbs and halluces, distal aphalangia, ectodermal anomalies, and poor outcome. Here, we report two sisters with YVS who also had papillo-macular atrophic chorioretinopathy with "salt-and-pepper" appearance that could not be attributed to environmental or metabolic causes. Our best hypothesis is that the ocular findings in our two patients are part of the phenotypic manifestations of YVS. We suggest that an extensive ophthalmologic examination should be carried out in all children with YVS in order to define the frequency and natur... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4057564 Sun, 03 Oct 2010 23:00:00 +0100 4057564 http://www.medworm.com/index.php?rid=4037534&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888932%26dopt%3DAbstract Authors: Mathis S, Maisonobe T, Neau JP Wolfram syndrome (WFS) is a degenerative disease with neurological and endocrine disorders, characterized by the association of juvenile diabetes mellitus and bilateral optic atrophy. A polyneuropathy was exceptionally described but its characteristics are not well-established. In addition to our observation, we searched all case reports of patients with WFS in the medical literature (more than 600), and selected patients who underwent an EMG: twenty-one patients underwent an EMG, which was considered as abnormal in only 8 cases. The common profile was axonal sensory-motor polyneuropathy, sometimes with marked decrease of motor conduction velocities. This neuropathy could be due to diabetes mellitus, even though microagiopathic and macroangiopath... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4037534 Wed, 29 Sep 2010 23:00:00 +0100 4037534 http://www.medworm.com/index.php?rid=4037533&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888933%26dopt%3DAbstract We describe here 11 adults with features of VACTERL association ascertained through our research study on the condition. In our cohort of adult patients, approximately 25% of medically significant malformations that are component features of VACTERL association, including 40% of vertebral, 50% of cardiac, and 50% of renal anomalies, were not identified during childhood. Additionally, medical sequelae of many of the primary malformations identified in infancy or early childhood persist or are first reported in adulthood. These sequelae can involve challenging medical and surgical management in adulthood. As most adults with VACTERL association are not specifically followed for VACTERL-related issues, a more uniform diagnostic work-up and a low threshold for investigation of medical sequelae... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4037533 Wed, 29 Sep 2010 23:00:00 +0100 4037533 http://www.medworm.com/index.php?rid=4037532&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888934%26dopt%3DAbstract We report identical twins who presented with polyhydramnios and loss of fetal motility during pregnancy; hypotonia, arthrogryposis and swallowing impairment at birth; need of immediate respiratory support and death at 27 and 50 days of life. Muscle biopsies, performed at 27 days of life in twin 1 and at 49 days in twin 2, showed the presence of separate cores and rods in the muscle fibres, both at light and electron microscopy. The molecular analysis showed a heterozygous de-novo mutation (Ile4898Thr) of the RYR1 gene. The molecular study of ACTA1, TMP2 and TMP3 genes did not show abnormalities. This is the first report of a lethal form of congenital "core-rod myopathy". The mutation Ile4898Thr has been previously described in central core disease but not in core-rod myopathy. The report e... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4037532 Wed, 29 Sep 2010 23:00:00 +0100 4037532 http://www.medworm.com/index.php?rid=4037531&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20888935%26dopt%3DAbstract Authors: Masurel-Paulet A, Haan E, Thompson EM, Goizet C, Thauvin-Robinet C, Tai A, Kennedy D, Smith G, Khong TY, Solé G, Guerineau E, Coupry I, Huet F, Robertson S, Faivre L X-linked periventricular nodular heterotopia (PH) is a neuronal migration disorder caused by mutations in the gene encoding filamin A (FLNA). High phenotypic diversity, ranging from PH to otopalatodigital syndrome and frontometaphyseal dysplasia has been described in association with FLNA mutations. Extra-neurological features including cardiovascular abnormalities, coagulopathy, skeletal dysplasia and joint hypermobility have sometimes been described in patients with PH. Respiratory manifestations have not been associated with FLNA disorders with the exception of tracheal stenosis and pulmonary hypoplasia associ... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4037531 Wed, 29 Sep 2010 23:00:00 +0100 4037531 http://www.medworm.com/index.php?rid=4037535&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20887823%26dopt%3DAbstract We report an adult male with 22q11.2 deletion syndrome and a germline BRCA2 mutation who developed T-cell monoclonal lymphoid proliferation involving the skin and a polyclonal proliferation of a retroperitoneal lymph node without any identifiable infectious and inflammatory causes. This is the first report of reactive lymphoid hyperplasia in the setting of co-occurrence of 22q11.2 deletion syndrome and a BRCA2 mutation. Further cases with a similar presentation should be reported and studies should be directed to identify the possible mechanisms involved. PMID: 20887823 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4037535 Mon, 27 Sep 2010 23:00:00 +0100 4037535 http://www.medworm.com/index.php?rid=4024214&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20870045%26dopt%3DAbstract We report a 797 kb de novo interstitial deletion of 18q21.31 in a 6-year-old boy with speech delay, mental retardation, sleeping problems, facial dysmorphism, and feet anomalies. Examination of the region showed two genes, TXNL1 and WDR7, to be involved in the deletion. Haploinsufficiency of these genes could potentially contribute to the phenotype. Our patient has some clinical features that overlap with earlier described patients with a larger deletion of the distal part of chromosome 18q. The small deletion in region 18q21.31 may be responsible for some of the common features found in patients with larger 18q deletions. PMID: 20870045 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=4024214 Wed, 22 Sep 2010 23:00:00 +0100 4024214 http://www.medworm.com/index.php?rid=3987571&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20849990%26dopt%3DAbstract This article highlights current perspectives on agnathia-otocephaly with a focus on the etiological causes and issues concerning prenatal diagnosis, differential diagnosis, prognosis and genetic counseling. Finally, studies using animal models especially genetically engineered mice are described to comprehend the molecular genetic interactions that may occur during the genesis of this intriguing craniofacial birth defect. PMID: 20849990 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3987571 Mon, 13 Sep 2010 23:00:00 +0100 3987571 http://www.medworm.com/index.php?rid=3987570&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20849991%26dopt%3DAbstract Authors: Schramm C, Draaken M, Bartels E, Boemers TM, Aretz S, Brockschmidt FF, Nöthen MM, Ludwig M, Reutter H The non-random association of vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with esophageal atresia (TE), renal malformations (R), and limb defects (L) is termed VACTERL association. The aim of the present study was to identify microaberrations characterized by a loss or gain of genomic material that contribute to VACTERL association at a genome-wide level. Molecular karyotyping was performed in a cohort of 12 patients with anorectal malformations and at least two additional cardinal features of the VACTERL association. A de novo microduplication at chromosomal region 22q11.21 was identified in a patient presenting with t... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3987570 Mon, 13 Sep 2010 23:00:00 +0100 3987570 http://www.medworm.com/index.php?rid=3969763&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20837174%26dopt%3DAbstract In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion. PMID: 20837174 [PubMed - as supplied by publisher] (Source: European Journal of Medical G... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3969763 Thu, 09 Sep 2010 23:00:00 +0100 3969763 http://www.medworm.com/index.php?rid=3969764&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20832509%26dopt%3DAbstract We report on a 6 and 9/12 year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably our patient, per formal IQ testing, was not found to have frank mental retardation as has been previously reported among patients with chromosome 3q29 terminal deletion, but rather our patient has demonstrated a... European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3969764 Tue, 07 Sep 2010 23:00:00 +0100 3969764 http://www.medworm.com/index.php?rid=3960673&cid=s_35543_50_f&fid=35543&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20826235%26dopt%3DAbstract We report a 15-day-old girl with partial trisomy 4q syndrome who presented with neonatal cholestasis. She had dysmorphic facial features and preaxial polysyndactyly of the right hand. The other findings were generalized hypertrichosis, pes equinovarus, oedema on feet and mild hepatomegaly. No specific reason for the cholestasis with elevated liver enzymes and direct bilirubinemia were characterized. Cytogenetic analyses revealed a karyotype 46,XX,der(13)t(4;13)(q25;p13). This is the first patient with partial trisomy 4q syndrome presented with neonatal cholestasis. PMID: 20826235 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics) European Journal of Medical Genetics journals http://www.medworm.com/rss/comments.php?id=3960673 Thu, 02 Sep 2010 23:00:00 +0100 3960673