| Contribution of VANGL2 mutations to isolated neural tube defects. | |
| | |
MedLine Citation:
|
PMID: 20738329 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non-canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi-ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations. |
| | |
Authors:
|
Z Kibar; S Salem; C M Bosoi; E Pauwels; P De Marco; E Merello; A G Bassuk; V Capra; P Gros |
Related Documents
:
|
16287139 - Identification and functional analysis of cited2 mutations in patients with congenital ... 18519639 - Vacterl/caudal regression/currarino syndrome-like malformations in mice with mutation i... 17497699 - Abnormal vertebral segmentation and the notch signaling pathway in man. 19884679 - Cleft lip and palate genetics and application in early embryological development. 12124729 - Exclusion of pitx2 mutations as a major cause of charge association. 17035249 - A mutation in the f-box gene, fbxo11, causes otitis media in the jeff mouse. 10710219 - Different distribution of hiv type 1 genetic variants in european patients with distinc... 22378279 - High prevalence of genetic variants previously associated with lqt syndrome in new exom... 20472869 - Transient leukoencephalopathy associated with x-linked charcot-marie-tooth disease. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-22 |
Journal Detail:
|
Title: Clinical genetics Volume: 80 ISSN: 1399-0004 ISO Abbreviation: Clin. Genet. Publication Date: 2011 Jul |
Date Detail:
|
Created Date: 2011-06-08 Completed Date: 2011-09-28 Revised Date: 2011-11-24 |
Medline Journal Info:
|
Nlm Unique ID: 0253664 Medline TA: Clin Genet Country: Denmark |
Other Details:
|
Languages: eng Pagination: 76-82 Citation Subset: IM |
Copyright Information:
|
© 2010 John Wiley & Sons A/S. |
Affiliation:
|
Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montreal, Montreal, Quebec, Canada. zoha.kibar@recherche-stejustine.qc.ca |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Female Genetic Predisposition to Disease Humans Intracellular Signaling Peptides and Proteins / genetics* Male Membrane Proteins / genetics* Molecular Sequence Data Mutation Mutation, Missense Neural Tube Defects / genetics*, pathology |
| Grant Support | |
ID/Acronym/Agency:
|
1R01 NS064159-01A1/NS/NINDS NIH HHS; GGP08051//Telethon; MT-13425//Canadian Institutes of Health Research; R01 NS064159-01A1/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/VANGL2 protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Novel homozygous mutation in DSP causing skin fragility-woolly hair syndrome: report of a large fami...
Next Document: Silver-Russell patients showing a broad range of ICR1 and ICR2 hypomethylation in different tissues.