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Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects

Authors :
L. Sabova
F. Horn
A. Thiede
H. Gocan
U. Zechner
Ina Kirmes
Oliver Bartsch
Thomas Haaf
Ioan Stefan Florian
S. Lechno
Source :
Molecular Syndromology. 3:76-81
Publication Year :
2012
Publisher :
S. Karger AG, 2012.

Abstract

Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system occurring at an average rate of 1 per 1,000 human pregnancies worldwide. Numerous genetic and environmental factors are discussed to be relevant in their etiology. In mice, mutants in >200 genes including the planar cell polarity (PCP) pathway are known to cause NTDs, and recently, heterozygous mutations in the human VANGL1 gene have been described in a small subset of patients with NTDs. We performed a VANGL1 mutation analysis in 144 unrelated individuals with NTDs from Slovakia, Romania and Germany and identified 3 heterozygous missense mutations: c.613G>A (p.Gly205Arg) with an open spina bifida (lumbosacral meningomyelocele), c.557G>A (p.Arg186His) with a closed spina bifida (tethered cord and spinal lipoma) and c.518G>A (p.Arg173His) with an unknown NTD. The c.613G>A mutation was also found in a healthy sibling. None of the mutations were described previously. Findings support that heterozygous VANGL1 mutations represent hypomorphs or conditional mutants predisposing to NTDs and occur at a frequency of approximately 2.1% of open and closed spinal NTDs. The mutations (p.Arg173His, p.Arg186His, p.Gly205Arg) modified conserved regions of the VANGL1 protein and shared similarities with previously described mutants, providing further evidence for the presence of mutational hot spots in these patients.

Details

ISSN :
16618777 and 16618769
Volume :
3
Database :
OpenAIRE
Journal :
Molecular Syndromology
Accession number :
edsair.doi...........a6a7fb0f86b7cd0293f14cc9528af63a
Full Text :
https://doi.org/10.1159/000339668