Contribution of VANGL2 mutations to isolated neural tube defects

Zoha Kibar; Sandra Salem; Ciprian M Bosoi; Elodie Pauwels; Patrizia De Marco; Elisa Merello; Alexander G Bassuk; Valeria Capra; Philippe Gros

doi:10.1111/j.1399-0004.2010.01515.x

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Contribution of VANGL2 mutations to isolated neural tube defects

Journal article

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Peer reviewed

Contribution of VANGL2 mutations to isolated neural tube defects

Zoha Kibar, Sandra Salem, Ciprian M Bosoi, Elodie Pauwels, Patrizia De Marco, Elisa Merello, Alexander G Bassuk, Valeria Capra and Philippe Gros

Clinical genetics, Vol.80(1), pp.76-82

07/2011

DOI: 10.1111/j.1399-0004.2010.01515.x

PMCID: PMC3000889

PMID: 20738329

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Abstract

Vangl2 was identified as the gene defective in the Looptail mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity 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 7 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.

planar cell polarity

neural tube defects

VANGL2

Details

Title: Subtitle: Contribution of VANGL2 mutations to isolated neural tube defects
Creators: Zoha Kibar - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montreal
Sandra Salem - Department of Biochemistry, McGill University, Montreal, QC, Canada
Ciprian M Bosoi - Department of Obstetrics and Gynecology, CHU Sainte Justine Research Center and University of Montreal
Elodie Pauwels - Department of Biochemistry, McGill University, Montreal, QC, Canada
Patrizia De Marco - U.O. Neurochirurgia, Istituto G. Gaslini, Genova, Italy
Elisa Merello - U.O. Neurochirurgia, Istituto G. Gaslini, Genova, Italy
Alexander G Bassuk - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Valeria Capra - U.O. Neurochirurgia, Istituto G. Gaslini, Genova, Italy
Philippe Gros - Department of Biochemistry, McGill University, Montreal, QC, Canada
Resource Type: Journal article
Publication Details: Clinical genetics, Vol.80(1), pp.76-82
DOI: 10.1111/j.1399-0004.2010.01515.x
PMID: 20738329
PMCID: PMC3000889
NLM abbreviation: Clin Genet
ISSN: 0009-9163
eISSN: 1399-0004
Language: English
Date published: 07/2011
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984020648202771

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