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Allelic imbalance (AI) identifies novel tissue-specific cis-regulatory variation for human UGT2B15Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we measured the relative expression of two alleles at this gene by using SNP rs1902023:G>T. An excess of the G over the T allele was consistently observed in liver (PT as the cis-regulatory variants; both SNPs were also evaluated in LNCaP and Caco-2 cells. By ChIP, we showed that the transcription factor Nrf2 binds to the region spanning rs34010522:G>T in all four cell lines. Our results provide a good example for how AI can be used to identify cis-regulatory variation and gain insights into the tissue specific regulation of gene expression. Hum Mutat 30:1-9, 2009. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - November 14, 2009 Category: Genetics & Stem Cells Authors: Chang Sun, Catherine Southard, David B. Witonsky, Olufunmilayo I. Olopade, Anna Di Rienzo Source Type: journals

Crigler-Najjar syndrome in The Netherlands: Identification of four novel UGT1A1 alleles, genotype-phenotype correlation, and functional analysis of 10 missense mutantsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we have analyzed 19 CN patients diagnosed in The Netherlands (18) and in Belgium (1), and have identified 14 different UGT1A1 mutations, four of which are novel. Two mutations were present in several unrelated patients, suggesting the presence of two founder effects in The Netherlands. In addition, we show linkage of the UGT1A1[lowast]28 promoter polymorphism (rs5719145insTA) to three structural mutations. Functional studies of partial active UGT1A1 mutants are limited. Therefore, we performed in vitro studies to determine the functional activity of seven missense mutants identified in this study and of three...
Source: Human Mutation - November 6, 2009 Category: Genetics & Stem Cells Authors: Nina Sneitz, Conny T. Bakker, Robert J. de Knegt, Dicky J.J. Halley, Moshe Finel, Piter J. Bosma Source Type: journals

Spectrum of PEX6 mutations in Zellweger syndrome spectrum patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The autosomal recessive Zellweger syndrome spectrum (ZSS) disorders comprise a main subgroup of the peroxisome biogenesis disorders. The ZSS disorders can be caused by mutations in any of 12 different currently identified PEX genes resulting in severe, often lethal, multi-systemic disorders. Defects in the PEX6 gene are the second most common cause for ZSS disorders. The encoded protein PEX6 belongs to the AAA ATPase family and contains two AAA cassettes and an AAA protein family signature. The PEX6 gene consists of 17 exons and previously mutations in the PEX6 gene were found to be scattered over all exons. We developed a...
Source: Human Mutation - October 30, 2009 Category: Genetics & Stem Cells Authors: Merel S. Ebberink, Janet Kofster, Ronald J.A. Wanders, Hans R. Waterham Source Type: journals

Congenital disorders of glycosylation: An update on defects affecting the biosynthesis of dolichol-linked oligosaccharidesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Defects in the biosynthesis of the oligosaccharide precursor for N-glycosylation lead to decreased occupancy of glycosylation sites and thereby to diseases known as congenital disorders of glycosylation (CDG). In the last 20 years, approximately 1,000 CDG patients have been identified presenting with multiple organ dysfunctions. This review sets the state of the art by listing all mutations identified in the 15 genes (PMM2, MPI, DPAGT1, ALG1, ALG2, ALG3, ALG9, ALG12, ALG6, ALG8, DOLK, DPM1, DPM3, MPDU1, and RFT1) that yield a deficiency of dolichol-linked oligosaccharide biosynthesis. The present analysis shows that most m...
Source: Human Mutation - October 28, 2009 Category: Genetics & Stem Cells Authors: Micha A. Haeuptle, Thierry Hennet Source Type: journals

A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumbEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Werner mesomelic syndrome (WMS) is an autosomal dominant disorder with unknown molecular etiology characterized by hypo- or aplasia of the tibiae in addition to the preaxial polydactyly (PPD) of the hands and feet and/or five-fingered hand with absence of thumbs. We show that point mutations of a specific nucleotide within the sonic hedgehog (SHH) regulatory region (ZRS) cause WMS. In a previously unpublished WMS family, we identified the causative G>A transition at position 404 of the ZRS, and in six affected family members of a second WMS family we found a 404G>C mutation of the ZRS. The 404G>A ZRS mutation is known as t...
Source: Human Mutation - October 21, 2009 Category: Genetics & Stem Cells Authors: Dagmar Wieczorek, Barbara Pawlik, Yun Li, Nurten A. Akarsu, Almuth Caliebe, Klaus J.W. May, Bernd Schweiger, Fernando R. Vargas, Sevim Balci, Gabriele Gillessen-Kaesbach, Bernd Wollnik Source Type: journals

Evaluation of SNPs in miR-146a, miR196a2 and miR-499 as low-penetrance alleles in German and Italian familial breast cancer casesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our data suggested lack of association between SNPs rs2910164, rs11614913 and rs3746444 and breast cancer risk, or age at breast cancer onset. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - October 20, 2009 Category: Genetics & Stem Cells Authors: Irene Catucci, Rongxi Yang, Paolo Verderio, Sara Pizzamiglio, Ludwig Heesen, Kari Hemminki, Christian Sutter, Barbara Wappenschmidt, Michelle Dick, Norbert Arnold, Peter Bugert, Dieter Niederacher, Alfons Meindl, Rita K. Schmutzler, Claus C. Bartram, Filo Source Type: journals

Clinically reported reterozygous mutations in the PINK1 kinase domain exert a gene dosage effectEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in the gene encoding phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) have been associated with the loss of dopaminergic neurons characteristic of familial and sporadic Parkinson disease. We developed an in vitro system of stable human dopaminergic neuronal cell lines coexpressing an equivalent copy of normal and mutant PINK1 to simulate "heterozygous" and "homozygous" states in patients. Mutants in the N-terminus, C-terminus, and kinase domain were generated and cloned into a two-gene mammalian expression vector to generate stable mammalian expression cell lines producing an equivalent copy number ...
Source: Human Mutation - October 20, 2009 Category: Genetics & Stem Cells Authors: Eng-King Tan, F. Shaffra Refai, Mobin Siddique, Karen Yap, Patrick Ho, Stephanie Fook-Chong, Yi Zhao Source Type: journals

Spectrum and consequences of SMC1A mutations: The unexpected involvement of a core component of cohesin in human diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
SMC1A encodes a structural component of the cohesin complex, which is necessary for sister chromatid cohesion. In addition to its canonical role, cohesin has been shown to be involved in gene expression regulation and maintenance of genome stability. Recently, it has been demonstrated that mutations in the SMC1A gene are responsible for Cornelia de Lange syndrome (CdLS). CdLS is a genetically heterogeneous multisystem developmental disorder with variable expressivity, typically characterized by consistent facial dysmorphia, upper extremity malformations, hirsutism, cardiac defects, growth and cognitive retardation, gastroi...
Source: Human Mutation - October 19, 2009 Category: Genetics & Stem Cells Authors: Linda Mannini, Jinglan Liu, Ian D. Krantz, Antonio Musio Source Type: journals

Multiple osteochondromas: mutation update and description of the multiple osteochondromas mutation database (MOdb)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple osteochondromas (MO) is an autosomal dominant skeletal disease characterized by the formation of multiple cartilage-capped bone tumors growing outward from the metaphyses of long tubular bones. MO is genetically heterogeneous, and is associated with mutations in Exostosin-1 (EXT1) or Exostosin-2 (EXT2), both tumor-suppressor genes of the EXT gene family. All members of this multigene family encode glycosyltransferases involved in the adhesion and/or polymerization of heparin sulfate (HS) chains at HS proteoglycans (HSPGs). HSPGs have been shown to play a role in the diffusion of Ihh, thereby regulating chondrocyte...
Source: Human Mutation - October 6, 2009 Category: Genetics & Stem Cells Authors: Ivy Jennes, Elena Pedrini, Monia Zuntini, Marina Mordenti, Sahila Balkassmi, Carla G. Asteggiano, Brett Casey, Bert Bakker, Luca Sangiorgi, Wim Wuyts Source Type: journals

Missense mutations of conserved glycine residues in fibrillin-1 highlight a potential subtype of cb-EGF-like domainsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In six index cases/families referred for Marfan syndrome (MFS) molecular diagnosis, we identified six novel mutations in the FBN1 gene: c.1753G>C (p.Gly585Arg), c.2456G>A (p.Gly819Glu), c.4981G>A (p.Gly1661Arg), c.5339G>A (p.Gly1780Glu), c.6418G>A (p.Gly2140Arg) and c.6419G>A (p.Gly2140Glu). These variants, predicted to result in Glycine substitutions are located at the third position of a 4 amino acids loop-region of calcium-binding Epidermal Growth Factor-like (cb-EGF) fibrillin-1 domains 5, 9, 24, 25 and 32. Familial segregation studies showing cosegregation with MFS manifestations or de novo inheritance in addition to ...
Source: Human Mutation - October 2, 2009 Category: Genetics & Stem Cells Authors: Philippe Khau Van Kien, David Baux, Nathalie Pallares-Ruiz, Corinne Baudoin, Aurélie Plancke, Nicolas Chassaing, Patrick Collignon, Valérie Drouin-Garraud, Alain Hovnanian, Dominique Martin-Coignard, Gwenaëlle Collod-Béroud, Christophe Béroud, Anne-F Source Type: journals

Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The human CYP1A1_CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head-to-head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60 CYP1A1_CYP1A2 SNPs found in the present study (eight New Guinea Highlanders, eight Samoans, four Dogrib, four Teribe, four Pehuenche, and one Caucasian) with those found in a previous st...
Source: Human Mutation - October 2, 2009 Category: Genetics & Stem Cells Authors: Lucia F. Jorge-Nebert, Zhengwen Jiang, Ranajit Chakraborty, Joanna Watson, Li Jin, Stephen T. McGarvey, Ranjan Deka, Daniel W. Nebert Source Type: journals

Recurrent copy number alterations in BRCA1-mutated ovarian tumors alter biological pathwaysEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Array CGH was used to identify recurrent copy number alterations (RCNA) characteristic of either BRCA1-related or sporadic ovarian cancer. After preprocessing, both groups of patients were modeled using a recurrent Hidden Markov Model to detect RCNA. RCNA with a probability higher than 80% were called. After removing RCNA present in both groups, the genes present in the remaining RCNA were investigated for enrichment of pathways from external databases. More RCNA were observed in the BRCA1 group, and they display more losses than gains compared to the sporadic group. When focusing on the type of RCNA, no significant differ...
Source: Human Mutation - October 2, 2009 Category: Genetics & Stem Cells Authors: Karin Leunen, Olivier Gevaert, Anneleen Daemen, Vanessa Vanspauwen, Geneviève Michils, Bart De Moor, Philippe Moerman, Ignace Vergote, Eric Legius Source Type: journals

A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) geneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition characterised by the presence of facial fibrofolliculomas, pulmonary cysts which may be associated with spontaneous pneumothorax and renal tumours. Germline mutations in the gene Folliculin (FLCN) were first identified in BHD patients in 2002. In addition FLCN mutations have also been described in families with isolated primary spontaneous pneumothorax (PSP) and also familial clear cell renal carcinomas (FcRCC). We have established a locus-specific database based on the Leiden Open (source) Variation Database (LOVD) software. The version of the database cont...
Source: Human Mutation - October 1, 2009 Category: Genetics & Stem Cells Authors: Derek H.K. Lim, Pauline K. Rehal, Michael S. Nahorski, Fiona Macdonald, Tijs Claessens, Michel Van Geel, Lieke Gijezen, Johan J.P. Gille, Sophie Giraud, Stephane Richard, Maurice van Steensel, Fred H. Menko, Eamonn R. Maher Source Type: journals

Functional redundancy of exon 12 of BRCA2 revealed by a comprehensive analysis of the c.6853A>G (p.I2285V) variantEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Variants of unknown significance (VUS) in BRCA1 and BRCA2 are common, and present significant challenges for genetic counseling. We observed that BRCA2: c.6853A>G (p.I2285V) (Breast Cancer Information Core [BIC] name: 7081A>G; ) co-occurs in trans with the founder mutation c.5946delT (p.S1982RfsX22) (BIC name: 6174delT), supporting the published classification of p.I2285V as a neutral variant. However, we also noted that when compared with wild-type BRCA2, p.I2285V resulted in increased exclusion of exon 12. Functional assay using allelic complementation in Brca2-null mouse embryonic stem cells revealed that p.I2285V, an a...
Source: Human Mutation - September 30, 2009 Category: Genetics & Stem Cells Authors: Lili Li, Kajal Biswas, Laura Anne Habib, Sergey G. Kuznetsov, Nancy Hamel, Tomas Kirchhoff, Nora Wong, Susan Armel, George Chong, Steven A. Narod, Kathleen Claes, Kenneth Offit, Mark E. Robson, Stacey Stauffer, Shyam K. Sharan, William D. Foulkes Source Type: journals

Structural aspects of therapeutic enzymes to treat metabolic disordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article is an overview of the correlation between structural perturbations of these enzymes with the clinical presentation of the respective metabolic conditions, as well as a discussion of the relevant structural modification strategies engaged in improving these enzymes for replacement therapies. Hum Mutat 30:1-20, 2009. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - September 29, 2009 Category: Genetics & Stem Cells Authors: Tse Siang Kang, Raymond C. Stevens Source Type: journals

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glucokinase is a key regulatory enzyme in the pancreatic beta-cell. It plays a crucial role in the regulation of insulin secretion and has been termed the glucose sensor in pancreatic beta-cells. Given its central role in the regulation of insulin release it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyper- and hypoglycemia. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young (MODY) subtype glucokinase (GCK), characterized by mild fasting hyperglycemia, which is present at birth but often only detected later in life during screening for other pur...
Source: Human Mutation - September 28, 2009 Category: Genetics & Stem Cells Authors: Kara K. Osbak, Kevin Colclough, Cecile Saint-Martin, Nicola L. Beer, Christine Bellanné-Chantelot, Sian Ellard, Anna L. Gloyn Source Type: journals

CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozy...
Source: Human Mutation - September 23, 2009 Category: Genetics & Stem Cells Authors: Soumaya Mougou-Zerelli, Sophie Thomas, Emmanuelle Szenker, Sophie Audollent, Nadia Elkhartoufi, Candice Babarit, Stéphane Romano, Rémi Salomon, Jeanne Amiel, Chantal Esculpavit, Marie Gonzales, Estelle Escudier, Bruno Leheup, Philippe Loget, Sylvie Oden Source Type: journals

A common variant in MTHFD1L is associated with neural tube defects and mRNA splicing efficiencyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polymorphisms in folate-related genes have emerged as important risk factors in a range of diseases including neural tube defects (NTDs), cancer, and coronary artery disease (CAD). Having previously identified a polymorphism within the cytoplasmic folate enzyme, MTHFD1, as a maternal risk factor for NTDs, we considered the more recently identified mitochondrial paralogue, MTHFD1L, as a candidate gene for NTD association. We identified a common deletion/insertion polymorphism, rs3832406, c.781-6823ATT(7-9), which influences splicing efficiency and is strongly associated with NTD risk. Three alleles of rs3832406 were detecte...
Source: Human Mutation - September 22, 2009 Category: Genetics & Stem Cells Authors: Anne Parle-McDermott, Faith Pangilinan, Kirsty K. O'Brien, James L. Mills, Alan M. Magee, James Troendle, Marie Sutton, John M. Scott, Peadar N. Kirke, Anne M. Molloy, Lawrence C. Brody Source Type: journals

ssSNPTarget: genome-wide splice-site single nucleotide polymorphism databaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Deep sequencing has shown that over 90% of human genes undergo alternative splicing. The splicing process requires exon-intron boundary recognition. SNPs located in the boundaries (splice sites) influence exon configuration. Also, splice site SNPs (ssSNPs) alter translation efficiency of the mRNA and lead to important changes in disease susceptibility. We developed the ssSNPTarget database to provide ssSNPs on human and mouse genes. It includes: 1) ssSNP distribution information in human and mouse genes; 2) effects of SNPs in splice sites: junction strength change, protein domain change, and alternative splicing events (ex...
Source: Human Mutation - September 16, 2009 Category: Genetics & Stem Cells Authors: Jin Ok Yang, Woo-Yeon Kim, Jong Bhak Source Type: journals

Genetic and cellular studies of oxidative stress in methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Methylmalonic aciduria (MMA) cobalamin deficiency type C (cblC) with homocystinuria (MMACHC) is the most frequent genetic disorder of vitamin B12 metabolism. The aim of this work was to identify the mutational spectrum in a cohort of cblC-affected patients and the analysis of the cellular oxidative stress and apoptosis processes, in the presence or absence of vitamin B12. The mutational spectrum includes nine previously described mutations: c.3G>A (p.M1L), c.217C>T (p.R73X), c.271dupA (p.R91KfsX14), c.331C>T (p.R111X), c.394C>T (p.R132X), c.457C>T (p.R153X), c.481C>T (p.R161X), c.565C>A (p.R189S), and c.615C>G (p.Y205X), a...
Source: Human Mutation - September 15, 2009 Category: Genetics & Stem Cells Authors: Eva Richard, Ana Jorge-Finnigan, Judit Garcia-Villoria, Begoña Merinero, Lourdes R. Desviat, Laura Gort, Paz Briones, Fátima Leal, Celia Pérez-Cerdá, Antonia Ribes, Magdalena Ugarte, Belén Pérez, the MMACHC Working Group Source Type: journals

Novel missense mutations in the FOXC2 gene alter transcriptional activityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations in the FOXC2 gene that codes for a forkhead transcription factor are associated with primary lymphedema that usually develops around puberty. Associated abnormalities include distichiasis and, very frequently, superficial and deep venous insufficiency. Most mutations reported so far either truncate the protein or are missense mutations in the forkhead domain causing a loss of function. The haplo-insufficient state is associated with lymphatic hyperplasia in mice as well as in humans. We analyzed the FOXC2 gene in 288 patients with primary lymphedema and found 11 pathogenic mutations, of which 9 are novel. Of thos...
Source: Human Mutation - September 15, 2009 Category: Genetics & Stem Cells Authors: M.A.M. van Steensel, R.J. Damstra, M. Heitink, R.S. Bladergroen, J. Veraart, Peter M. Steijlen, M. van Geel Source Type: journals

The pharmacological chaperone 1-deoxynojirimycin increases the activity and lysosomal trafficking of multiple mutant forms of acid alpha-glucosidaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we characterized the pharmacological chaperone 1-deoxynojirimycin (DNJ) on 76 different mutant forms of GAA identified in Pompe disease. DNJ significantly increased enzyme activity and protein levels for 16 different GAA mutants in patient-derived fibroblasts and in transiently transfected COS-7 cells. Additionally, DNJ increased the processing of these GAA mutants to their mature lysosomal forms, suggesting facilitated trafficking through the secretory pathway. Immunofluorescence microscopy studies showed increased colocalization of GAA with the lysosomal marker LAMP2 after incubation with DNJ, confirming i...
Source: Human Mutation - September 4, 2009 Category: Genetics & Stem Cells Authors: John J. Flanagan, Barbara Rossi, Katherine Tang, Xiaoyang Wu, Kirsten Mascioli, Francesca Donaudy, Maria Rosaria Tuzzi, Federica Fontana, Maria Vittoria Cubellis, Caterina Porto, Elfrida Benjamin, David J. Lockhart, Kenneth J. Valenzano, Generoso Andria, Source Type: journals

Mutation spectrum of homogentisic acid oxidase (HGD) in alkaptonuriaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides valuable resources for molecular analysis of alkaptonuria and expands our knowledge of the molecular basis of this disease. Hum Mutat 30:1-9, 2009. Published 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - September 4, 2009 Category: Genetics & Stem Cells Authors: Thierry Vilboux, Michael Kayser, Wendy Introne, Pim Suwannarat, Isa Bernardini, Roxanne Fischer, Kevin O'Brien, Robert Kleta, Marjan Huizing, William A. Gahl Source Type: journals

Deep sequencing to reveal new variants in pooled DNA samplesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We describe custom bioinformatics and statistics to optimize detection of rare variants and to estimate required sequencing depth. Our results provide directions for designing high-throughput analyses of candidate genes. Hum Mutat 30:1-10, 2009. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - September 3, 2009 Category: Genetics & Stem Cells Authors: Astrid A. Out, Ivonne J.H.M. van Minderhout, Jelle J. Goeman, Yavuz Ariyurek, Stephan Ossowski, Korbinian Schneeberger, Detlef Weigel, Michiel van Galen, Peter E.M. Taschner, Carli M.J. Tops, Martijn H. Breuning, Gert-Jan B. van Ommen, Johan T. den Dunnen Source Type: journals

Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHDEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, we describe two ways to develop FSHD: (1) contraction-dependent or (2) contraction-independent D4Z4 hypomethylation on the 4qA161 subtelomere. Hum Mutat 30:1-11, 2009. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - September 3, 2009 Category: Genetics & Stem Cells Authors: Jessica C. de Greef, Richard J.L.F. Lemmers, Baziel G.M. van Engelen, Sabrina Sacconi, Shannon L. Venance, Rune R. Frants, Rabi Tawil, Silvère M. van der Maarel Source Type: journals

Pseudoexon exclusion by antisense therapy in methylmalonic aciduria (MMAuria)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Development of pseudoexon exclusion therapies by antisense modification of pre-mRNA splicing represents a type of personalized genetic medicine. Here we present the cellular antisense therapy and the cell-based splicing assays to investigate the effect of two novel deep intronic changes c.1957-898A>G and c.1957-920C>A identified in the methylmalonyl-coenzyme A (CoA) mutase (MUT) gene. The results show that the nucleotide change c.1957-898A>G is a pathological mutation activating pseudoexon insertion and that antisense morpholino oligonucleotide (AMO) treatment in patient fibroblasts leads to recovery of MUT activity to lev...
Source: Human Mutation - September 2, 2009 Category: Genetics & Stem Cells Authors: B. Pérez, A. Rincón, A. Jorge-Finnigan, E. Richard, B. Merinero, M. Ugarte, L.R. Desviat Source Type: journals

Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts hedgehog signalingEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autosomal recessive Ellis-van Creveld syndrome and autosomal dominant Weyer acrodental dysostosis are allelic conditions caused by mutations in EVC or EVC2. We performed a mutation screening study in 36 EvC cases and 3 cases of Weyer acrodental dysostosis, and identified pathogenic changes either in EVC or in EVC2 in all cases. We detected 40 independent EVC/EVC2 mutations of which 29 were novel changes in Ellis-van Creveld cases and 2 were novel mutations identified in Weyer pedigrees. Of interest one EvC patient had a T>G nucleotide substitution in intron 7 of EVC (c.940-150T>G), which creates a new donor splice site and...
Source: Human Mutation - September 1, 2009 Category: Genetics & Stem Cells Authors: Maria Valencia, Pablo Lapunzina, Derek Lim, Raffaella Zannolli, Deborah Bartholdi, Bernd Wollnik, Othman Al-Ajlouni, Suhair S. Eid, Helen Cox, Sabrina Buoni, Joseph Hayek, Maria L. Martinez-Frias, Perez-Aytes Antonio, Samia Temtamy, Mona Aglan, Judith A. Source Type: journals

Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemiaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The primary pathology in many cases of myelodysplasia (MDS) and acute myeloid leukemia (AML) remains unknown. In some cases, two or more affected members have been identified in the same family. To date, mutations in two genes have been directly implicated: the hematopoietic transcription factors RUNX1 (runt-related transcription factor 1) and CEBPA (CCATT-box enhancer binding protein [alpha]). However, there are also other familial cases of MDS/AML where the genetic basis remains unknown. Both MDS, and to a lesser extent AML, have been observed in cases of the bone marrow failure syndrome dyskeratosis congenita, in which ...
Source: Human Mutation - September 1, 2009 Category: Genetics & Stem Cells Authors: Michael Kirwan, Tom Vulliamy, Anna Marrone, Amanda J. Walne, Richard Beswick, Peter Hillmen, Richard Kelly, Andrew Stewart, David Bowen, Stefan O. Schonland, Annika Maria Whittle, Anthony McVerry, Maria Gilleece, Inderjeet Dokal Source Type: journals

Two-round coamplification at lower denaturation temperature-PCR (COLD-PCR)-based sanger sequencing identifies a novel spectrum of low-level mutations in lung adenocarcinomaEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Reliable identification of cancer-related mutations in TP53 is often problematic, as these mutations can be randomly distributed throughout numerous codons and their relative abundance in clinical samples can fall below the sensitivity limits of conventional sequencing. To ensure the highest sensitivity in mutation detection, we adapted the recently described coamplification at lower denaturation temperature-PCR (COLD-PCR) method to employ two consecutive rounds of COLD-PCR followed by Sanger sequencing. Using this highly sensitive approach we screened 48 nonmicrodissected lung adenocarcinoma samples for TP53 mutations. Tw...
Source: Human Mutation - September 1, 2009 Category: Genetics & Stem Cells Authors: Jin Li, Coren A. Milbury, Cheng Li, G. Mike Makrigiorgos Source Type: journals

Pathogenic mitochondrial tRNA mutations - which mutations are inherited and why?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest mitochondrial (mtDNA) mutations to cause human disease. The majority of mt-tRNA mutations are heteroplasmic and while some exhibit maternal transmission within families, many others are only seen as sporadic mutations. Using the available clinical, biochemical and genetic data from published pathogenic mt-tRNA mutations, we have explored several different factors thought to influence the transmission of mt-tRNA mutations. Our data show that the most important factor in predicting whether a mutation is transmitted to offspring is whether the mt-tRNA mutation i...
Source: Human Mutation - August 29, 2009 Category: Genetics & Stem Cells Authors: Joanna L. Elson, Helen Swalwell, Emma L. Blakely, Robert McFarland, Robert W. Taylor, Doug M. Turnbull Source Type: journals

Antisense oligonucleotide treatment for a pseudoexon-generating mutation in the NPC1 gene causing Niemann-Pick type C diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Niemann-Pick type C disease is an autosomal recessive disorder caused by mutations in either the NPC1 or NPC2 gene. While most of the mutations are missense, a few splicing mutations have also been described. We identified and characterized a novel point mutation c.1554-1009G>A located in intron 9 of the NPC1 gene in a Spanish patient. Sequencing of the cDNA from the patient showed that this intronic mutation creates a cryptic donor splice site resulting in the incorporation of 194 bp of intron 9 as a new exon (pseudoexon) in the mRNA. This new transcript bears a premature termination codon and is degraded by the nonsense-...
Source: Human Mutation - August 29, 2009 Category: Genetics & Stem Cells Authors: Laura Rodríguez-Pascau, Maria Josep Coll, Lluïsa Vilageliu, Daniel Grinberg Source Type: journals

NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
NR2E3, also called photoreceptor-specific nuclear receptor (PNR), is a transcription factor of the nuclear hormone receptor superfamily whose expression is uniquely restricted to photoreceptors. There, its physiological activity is essential for proper rod and cone photoreceptor development and maintenance. Thirty-two different mutations in NR2E3 have been identified in either homozygous or compound heterozygous state in the recessively inherited enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), and clumped pigmentary retinal degeneration (CPRD). The clinical phenotype common to all these patients...
Source: Human Mutation - August 28, 2009 Category: Genetics & Stem Cells Authors: Daniel F. Schorderet, Pascal Escher Source Type: journals

Repulsion between Lys258 and upstream arginines explains the missorting of the AQP2 mutant p.Glu258Lys in nephrogenic diabetes insipidusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, our data reveal that the RRRxxxKL motif and repulsion between K258 and the arginine-triplet within this motif are the primary cause of missorting of AQP2-E258K in NDI. Hum Mutat 30:1-10, 2009. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - August 22, 2009 Category: Genetics & Stem Cells Authors: Erik-Jan Kamsteeg, Monique Stoffels, Grazia Tamma, Irene B.M. Konings, Peter M.T. Deen Source Type: journals

Closely spaced multiple mutations as potential signatures of transient hypermutability in human genesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Data from diverse organisms suggests that transient hypermutability is a general mutational mechanism with the potential to generate multiple synchronous mutations, a phenomenon probably best exemplified by closely spaced multiple mutations (CSMMs). Here we have attempted to extend the concept of transient hypermutability from somatic cells to the germline, using human inherited disease-causing multiple mutations as a model system. Employing stringent criteria for data inclusion, we have retrospectively identified numerous potential examples of pathogenic CSMMs that exhibit marked similarities to the CSMMs reported in othe...
Source: Human Mutation - August 14, 2009 Category: Genetics & Stem Cells Authors: Jian-Min Chen, Claude Férec, David N. Cooper Source Type: journals

Shadow autozygosity mapping by linkage exclusion (SAMPLE): A simple strategy to identify the genetic basis of lethal autosomal recessive disordersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Autozygosity mapping has been invaluable for determining the genetic basis of lethal autosomal recessive disorders, but this approach remains challenging because DNA from affected individuals may often be unavailable or of insufficient quality for extensive molecular genetic studies. To circumvent these difficulties, we developed a computer program called "SAMPLE" (for shadow autozygosity mapping by linkage exclusion) to enhance autozygosity mapping through the empirical analysis of haplotypes of unaffected individuals in consanguineous families. Single nucleotide polymorphism (SNP) genotyping of unaffected individuals in ...
Source: Human Mutation - August 13, 2009 Category: Genetics & Stem Cells Authors: Ian M. Carr, Katarzyna Szymanska, Eamonn Sheridan, Alexander F. Markham, David T. Bonthron, Colin A. Johnson Source Type: journals

Mutation within TARDBP leads to Frontotemporal Dementia without motor neuron diseaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that a pathogenetic TARDBP mutation is causative of behavioural variant FTD (bvFTD). An aged woman in her seventies initially started to present apathy and depression associated with impairment in executive functions. The diagnosis of bvFTD (apathetic syndrome) was accomplished by three-year follow-up, and structural and functional neuroimaging. By five-years after onset, extensive electrophysiological investigations excluded subclinical motor neuron disease. In this patient, a single base substitution c.800A>G of TARDBP gene was identified. This mutation, already described as causative of ALS, predicted the amin...
Source: Human Mutation - August 4, 2009 Category: Genetics & Stem Cells Authors: B. Borroni, C. Bonvicini, A. Alberici, E. Buratti, C. Agosti, S. Archetti, A. Papetti, C. Stuani, M. Di Luca, M. Gennarelli, A. Padovani Source Type: journals

Mutation of ACTA2 gene as an important cause of familial and nonfamilial nonsyndromatic thoracic aortic aneurysm and/or dissection (TAAD)Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Approximately 20% of aortic aneurysm and/or dissection (AAD) cases result from inherited disorders, including several systemic and syndromatic connective-tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome, which are caused by mutations in the FBN1, COL3A1, and TGFBR1 and TGFBR2 genes, respectively. Nonsyndromatic AAD also has a familial background, and mutations of the ACTA2 gene were recently shown to cause familial AAD. In the present study, we conducted sequence analyses of the ACTA2 gene in 14 unrelated Japanese patients with familial thoracic AAD (TAAD), and in 26 with sporadic...
Source: Human Mutation - July 29, 2009 Category: Genetics & Stem Cells Authors: Hiroko Morisaki, Koichi Akutsu, Hitoshi Ogino, Norihiro Kondo, Itaru Yamanaka, Yoshiaki Tsutsumi, Tsuyoshi Yoshimuta, Toshiya Okajima, Hitoshi Matsuda, Kenji Minatoya, Hiroaki Sasaki, Hiroshi Tanaka, Hatsue Ishibashi-Ueda, Takayuki Morisaki Source Type: journals

Molecular characterization of 22 novel UDP-N-acetylglucosamine-1-phosphate transferase [alpha]- and [beta]-subunit (GNPTAB) gene mutations causing mucolipidosis types II[alpha]/[beta] and III[alpha]/[beta] in 46 patientsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study of mutations in the GNPTAB gene, the largest yet reported, extends our knowledge of the mutational heterogeneity evident in MLII[alpha]/[beta]/MLIII[alpha]/[beta]. © 2009 Wiley-Liss, Inc. (Source: Human Mutation)
Source: Human Mutation - July 24, 2009 Category: Genetics & Stem Cells Authors: Barbara Tappino, Nadia A. Chuzhanova, Stefano Regis, Andrea Dardis, Fabio Corsolini, Marina Stroppiano, Emmanuel Tonoli, Tommaso Beccari, Camillo Rosano, Jan Mucha, Mariana Blanco, Marina Szlago, Maja Di Rocco, David N. Cooper, Mirella Filocamo Source Type: journals

Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report here the first CNM mutation (c.1948G>A, p.E650 K) in the DNM2 GTPase effector domain (GED), leading to a slowly progressive moderate myopathy. COS7 cells transfected with DNM2 constructs harboring a disease-associated mutation in MD, PH, or GED show a reduced uptake of transferrin and low-density lipoprotein (LDL) complex, two markers of clathrin-mediated receptor endocytosis. A decrease in clathrin-mediated endocytosis was also identified in skin fibroblasts from one CNM patient. We studied the impact of DNM2 mutant overexpression on epidermal growth factor (EGF)-induced extracellular signal-regulated kinase 1 (...
Source: Human Mutation - July 20, 2009 Category: Genetics & Stem Cells Authors: Marc Bitoun, Anne-Cécile Durieux, Bernard Prudhon, Jorge A. Bevilacqua, Adrien Herledan, Vehary Sakanyan, Andoni Urtizberea, Luis Cartier, Norma B. Romero, Pascale Guicheney Source Type: journals

Extremely low risk of pheochromocytomas in complete VHL gene deletion casesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No Abstract (Source: Human Mutation)
Source: Human Mutation - July 19, 2009 Category: Genetics & Stem Cells Authors: Ram[umacr]nas Janavi[ccaron]ius, Robertas Adomaitis, Feliksas Jankevi[ccaron]ius, Laimonas Gri[scaron]kevi[ccaron]ius Source Type: journals

Response to: extremely low risk of pheochromocytomas in complete VHL gene deletion casesEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
No Abstract (Source: Human Mutation)
Source: Human Mutation - July 19, 2009 Category: Genetics & Stem Cells Authors: Gerlind Franke, Gerd Scherer, Hartmut P.H. Neumann Source Type: journals

Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer riskEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study investigated whether functional variations in FEN1 gene are associated with DNA damage and lung cancer risk. Thirty DNA samples were sequenced to identify variants and function of the variants was examined by a set of biochemical assays. DNA damage levels were detected by comet assays in a cohort of 303 coke-oven workers and 297 controls. The association with lung cancer risk was examined in two independent case-control panels consisted of a total 1,840 lung cancer patients and 1,958 controls. We identified two single nucleotide polymorphisms (SNPs) located in the FEN1 promoter c.-69G>A (rs174538:G>A) and 3[prim...
Source: Human Mutation - July 16, 2009 Category: Genetics & Stem Cells Authors: Ming Yang, Huan Guo, Chen Wu, Yuefeng He, Dianke Yu, Li Zhou, Fang Wang, Jian Xu, Wen Tan, Guanghai Wang, Binghui Shen, Jing Yuan, Tangchun Wu, Dongxin Lin Source Type: journals

EYA4, deleted in a case with middle interhemispheric variant of holoprosencephaly, interacts with SIX3 both physically and functionallyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Holoprosencephaly (HPE) is the most common congenital malformation of the developing human forebrain, in which the two cerebral hemispheres fail to separate to various degrees. Although pathological mutations have been identified in up to nine genes, a number of other genes as well as environmental factors are likely to be involved in HPE. Here, we describe a case with the middle interhemispheric variant, a milder variant of HPE, carrying a deletion of [sim]10.4 Mb at 6q22.31-q23.2, which includes the EYA4 gene. EYA4 is one of four vertebrate orthologs of the Drosophila melanogaster gene, eyes absent. EYA4 was co-immunopre...
Source: Human Mutation - July 15, 2009 Category: Genetics & Stem Cells Authors: Yuichi Abe, Akira Oka, Masashi Mizuguchi, Takashi Igarashi, Shumpei Ishikawa, Hiroyuki Aburatani, Shigetoshi Yokoyama, Hiroshi Asahara, Kazuaki Nagao, Masao Yamada, Toshiyuki Miyashita Source Type: journals

The APC Variant p.Glu1317Gln Predisposes to Colorectal Adenomas by a Novel Mechanism of Relaxing the Target for Tumorigenic Somatic APC MutationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Multiple rare nonsynonymous variants in APC predispose to colorectal adenomas. The mechanisms through which such variants act have been unclear, but it has been proposed that a specific ("just-right") level of [beta]-catenin signaling is required for colorectal tumorigenesis. This appears to be mediated by selection for APC genotypes that retain one, or rarely two, 20 amino acid [beta]-catenin downregulating repeats (20AARs). We investigated the mechanism through which the variant p.Glu1317Gln (c.3949G>C) contributes to colorectal tumorigenesis. We compared the patterns of somatic APC mutations in tumors from patients with...
Source: Human Mutation - July 14, 2009 Category: Genetics & Stem Cells Authors: Anthony R. Dallosso, Siân Jones, Duncan Azzopardi, Valentina Moskvina, Nada Al-Tassan, Geraint T. Williams, Shelley Idziaszczyk, D. Rhodri Davies, Peter Milewski, Sally Williams, John Beynon, Julian R. Sampson, Jeremy P. Cheadle Source Type: journals

SMC1A expression and mechanism of pathogenicity in probands with X-Linked Cornelia de Lange syndromeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cornelia de Lange Syndrome (CdLS) is a dominantly inherited heterogeneous genetic disorder with multisystem abnormalities. Sixty percent of probands with CdLS have heterozygous mutations in the Nipped-B-like (NIPBL) gene, 5% have mutations in the SMC1A gene, and one proband was found to have a mutation in the SMC3 gene. Cohesin is a multisubunit complex consisting of a SMC1A and SMC3 heterodimer and two non-SMC subunits. SMC1A is located on the human X chromosome and is reported to escape X inactivation. Twenty-nine unrelated CdLS probands with 21 unique SMC1A mutations have been identified including seven males. All mutat...
Source: Human Mutation - July 14, 2009 Category: Genetics & Stem Cells Authors: Jinglan Liu, Rachel Feldman, Zhe Zhang, Matthew A. Deardorff, Eden V. Haverfield, Maninder Kaur, Jennifer R. Li, Dinah Clark, Antonie D. Kline, Darrel J. Waggoner, Soma Das, Laird G. Jackson, Ian D. Krantz Source Type: journals

Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Metachromatic Leukodystrophy (MLD) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The disease manifests itself with a broad spectrum of clinical variants, all characterized by progressive neurodegeneration in the central and peripheral nervous systems. The correlation between mutations in the ARSA gene, residual enzymatic activity associated with the mutated alleles and patients' phenotype, which has been extensively drawn for common ARSA mutations, has recently been expanded to rare ones. In this context, functional studies on the rare allelic variances acquire particula...
Source: Human Mutation - July 14, 2009 Category: Genetics & Stem Cells Authors: Martina Cesani, Alessia Capotondo, Tiziana Plati, Lucia Sergi Sergi, Francesca Fumagalli, Maria Grazia Roncarolo, Luigi Naldini, Giancarlo Comi, Maria Sessa, Alessandra Biffi Source Type: journals

Microdeletion/duplication at the Xq28 IP locus causes a de novo IKBKG/NEMO/IKKgamma exon4_10 deletion in families with incontinentia pigmentiEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Incontinentia Pigmenti (IP) locus contains the IKBKG/NEMO/IKKgamma gene and its truncated pseudogene copy, IKBKGP/deltaNEMO. The major genetic defect in IP is a heterozygous exon4_10 IKBKG deletion (IKBKGdel) caused by a recombination between two consecutive MER67B repeats. We analyzed 91 IP females carrying the IKBKGdel, 59 of whom carrying de novo mutations (65%). In eight parents, we found two recurrent nonpathological variants of IP locus, which were also present as rare polymorphism in control population: the IKBKGPdel, corresponding to the exon4_10 deletion in the pseudogene, and the MER67Bdup, that replicates th...
Source: Human Mutation - July 14, 2009 Category: Genetics & Stem Cells Authors: Fusco Francesca, Paciolla Mariateresa, Pescatore Alessandra, Lioi Maria Brigida, Ayuso Carmen, Faravelli Francesca, Gentile Mattia, Zollino Marcella, D'Urso Michele, Miano Maria Giuseppina, Ursini Matilde Valeria Source Type: journals

Exon skipping-mediated dystrophin reading frame restoration for small mutationsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study we tested the feasibility of the exon skipping approach for patients with small mutations in in-frame exons. We first identified 54 disease-causing point mutations. We selected five patients with nonsense or frameshifting mutations in exons 10, 16, 26, 33, and 34. Wild-type and mutation specific 2[prime]OMePS AONs were tested in cell-free splicing assays and in cultured cells derived from the selected patients. The obtained results confirm cell-free splicing assay as an alternative system to test exon skipping propensity when patients' cells are unavailable. In myogenic cells, similar levels of exon skipping ...
Source: Human Mutation - July 13, 2009 Category: Genetics & Stem Cells Authors: Pietro Spitali, Paola Rimessi, Marina Fabris, Daniela Perrone, Sofia Falzarano, Matteo Bovolenta, Cecilia Trabanelli, Lara Mari, Elena Bassi, Sylvie Tuffery, Francesca Gualandi, Nadir M. Maraldi, Patrizia Sabatelli-Giraud, Alessandro Medici, Luciano Merli Source Type: journals

The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesisEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mutations within either the SHH gene or its related pathway components are the most common, and best understood, pathogenetic changes observed in holoprosencephaly patients; this fact is consistent with the essential functions of this gene during forebrain development and patterning. Here we summarize the nature and types of deleterious sequence alterations among over one hundred distinct mutations in the SHH gene (64 novel mutations) and compare these to over a dozen mutations in disease-related Hedgehog family members IHH and DHH. This combined structural analysis suggests that dysfunction of Hedgehog signaling in human ...
Source: Human Mutation - July 13, 2009 Category: Genetics & Stem Cells Authors: Erich Roessler, Kenia B. El-Jaick, Christèle Dubourg, Jorge I. Vélez, Benjamin D. Solomon, Daniel E. Pineda-Álvarez, Felicitas Lacbawan, Nan Zhou, Maia Ouspenskaia, Aimée Paulussen, Hubert J. Smeets, Ute Hehr, Claude Bendavid, Sherri Bale, Sylvie Oden Source Type: journals

The SCN1A variant database: a novel research and diagnostic toolEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The neuronal voltage-gated sodium channel Nav1.1 encoded by the SCN1A gene plays an important role in the generation and propagation of action potentials in the central nervous system. Altered function of this channel due to mutations in SCN1A leads to hypersynchronous neuronal discharges resulting in seizures or migrainous attaques. A large number of distinct sequence variants in SCN1A are associated with diverse epilepsy and migraine syndromes. We developed an online and freely available database containing all reported sequence variants in SCN1A (). We verified 623 distinct sequence variants, listed them using standard ...
Source: Human Mutation - July 7, 2009 Category: Genetics & Stem Cells Authors: Lieve RF Claes, Liesbet Deprez, Arvid Suls, Jonathan Baets, Katrien Smets, Tine Van Dyck, Tine Deconinck, Albena Jordanova, Peter De Jonghe Source Type: journals