X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family
X-linked mental retardation and autism are associated with a mutation in the NLGN4 gene, a member of the neuroligin family
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DOI：
10.1086/382137
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发表时间：
2004-03-01
影响因子：
9.8
通讯作者：
Briault, S
中科院分区：
文献类型：
--
作者：
Laumonnier, F;Bonnet-Brilhault, F;Briault, S
一个大的法国家庭，包括受影响男性患者的非特异性X连接智力智能受影响的成员，患有或没有自闭症或普遍性发育障碍，在神经素4基因（NLGN4）中具有2-基本对的缺失。 XP22.33。该突变导致正常蛋白序列中间的过早终止密码子，被认为可以抑制跨膜结构域和对神经素二聚体重要的序列，而神经素的二聚体很重要，而神经素的二聚化，这是通过与β-Neurexin结合结合的适当细胞 - 细胞相互作用所必需的。由于神经素在兴奋性突触中大多富集，因此这些结果表明突触发生的缺陷可能导致认知发展和交流过程中的缺陷。删除在自闭症和非自然主义智障男性中都存在的事实表明，NLGN4基因不仅参与自闭症，如先前所述，而且智力低下，这表明某些类型的自闭症和智力迟缓可能有普遍遗传起源。
A large French family including members affected by nonspecific X-linked mental retardation, with or without autism or pervasive developmental disorder in affected male patients, has been found to have a 2-base-pair deletion in the Neuroligin 4 gene (NLGN4) located at Xp22.33. This mutation leads to a premature stop codon in the middle of the sequence of the normal protein and is thought to suppress the transmembrane domain and sequences important for the dimerization of neuroligins that are required for proper cell-cell interaction through binding to beta-neurexins. As the neuroligins are mostly enriched at excitatory synapses, these results suggest that a defect in synaptogenesis may lead to deficits in cognitive development and communication processes. The fact that the deletion was present in both autistic and nonautistic mentally retarded males suggests that the NLGN4 gene is not only involved in autism, as previously described, but also in mental retardation, indicating that some types of autistic disorder and mental retardation may have common genetic origins.