Contribution of VANGL2 mutations to isolated neural tube defects.
Contribution of VANGL2 mutations to isolated neural tube defects.
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DOI：
10.1111/j.1399-0004.2010.01515.x
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发表时间：
2011-07
影响因子：
3.5
通讯作者：
Gros P
中科院分区：
文献类型：
--
作者：
Kibar Z;Salem S;Bosoi CM;Pauwels E;De Marco P;Merello E;Bassuk AG;Capra V;Gros P
Vangl 2被鉴定为神经管缺陷（NTD）的环尾小鼠模型中的基因缺陷。该基因形成平面细胞极性途径的一部分，也称为非典型卷曲/紊乱途径，其介导脊椎动物中正确原肠胚形成和神经管形成所必需的会聚延伸的形态发生过程。PCP信号传导中的遗传缺陷与小鼠模型中的NTD密切相关。为了评估VANGL 2在人类NTD复杂病因学中的作用，我们对673例家族性和散发性NTD患者的大型多种族队列中的该基因进行了重新测序，其中包括453例开放性脊柱裂和202例闭合性脊柱NTD病例。在7例患者中发现了6种新的罕见错义突变，其中5例受闭合性脊柱NTD影响。这表明，VANGL 2突变可能在约2.5%的闭合性脊柱NTD（202例中有5例）中易患NTD，其频率与开放性脊柱裂患者中检测到的0.4%（453例中有2例）的频率显著不同（P=0.027）。我们的研究结果强烈暗示VANGL 2在一个子集的患者脊髓NTD的遗传原因，并提供了额外的证据PCP信号在这些畸形的致病作用。
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.
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影响因子：
158.5
作者：
Kibar, Zoha;Torban, Elena;Gros, Philippe
通讯作者：
Gros, Philippe
影响因子：
14.9
作者：
Ehrich, M;Böcker, S;van den Boom, D
通讯作者：
van den Boom, D
DOI：
10.1016/0140-6736(91)90133-a
发表时间：
1991-07-20
期刊：
Lancet (London, England)
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0712126105
发表时间：
2008-03-04
影响因子：
11.1
作者：
Torban, Elena;Patenaude, Anne-Marie;Gros, Philippe
通讯作者：
Gros, Philippe
影响因子：
3.3
作者：
Rossi, A;Biancheria, R;Tortori-Donati, P
通讯作者：
Tortori-Donati, P