Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects
Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects
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DOI：
10.1159/000339668
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发表时间：
2012-01-01
影响因子：
1.1
通讯作者：
Horn, F.
中科院分区：
文献类型：
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作者：
Bartsch, O.;Kirmes, I.;Horn, F.
神经管缺陷（NTD）是一组中枢神经系统的先天性畸形，在全球范围内的平均发病率为每1,000例妊娠中有1例。许多遗传和环境因素进行了讨论，是相关的病因。在小鼠中，已知包括平面细胞极性（PCP）通路在内的1200个基因的突变导致NTD，最近，在一小部分NTD患者中描述了人VANGL 1基因的杂合突变。我们对来自斯洛伐克、罗马尼亚和德国的144名无亲缘关系的NTD患者进行了VANGL 1突变分析，并鉴定了3种杂合错义突变：c.613G>A（p.Gly205Arg）伴开放性脊柱裂（腰骶部脊膜脊髓膨出），c.613G>A（p.Gly205Arg）伴开放性脊柱裂（腰骶部脊膜脊髓膨出），c.613G> A（p.Gly205Arg）伴开放性脊柱裂（腰骶部脊膜脊髓膨出）。557 G>A（p.Arg186His）伴闭合性脊柱裂（脊髓栓系和脊髓脂肪瘤）和c. 518 G>A（p.Arg173His），NTD未知。梭613 G>在一个健康同胞中也发现了突变。以前没有描述过突变。研究结果支持杂合子VANGL 1突变代表了NTD易感性的亚型或条件突变，发生频率约为2.1%。
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 1 200 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