Novel De Novo SHANK3 Mutation in Autistic Patients
Novel De Novo SHANK3 Mutation in Autistic Patients
复制标题
DOI：
10.1002/ajmg.b.30822
复制
发表时间：
2009-04-05
影响因子：
2.8
通讯作者：
Rouleau, Guy A.
中科院分区：
文献类型：
--
作者：
Gauthier, Julie;Spiegelman, Dan;Rouleau, Guy A.
许多研究证实，遗传因素在自闭症谱系障碍(ASD)中起着重要作用。最近，突触支架蛋白SHANK3基因的从头突变与ASD表型有关。作为我们基因发现策略的一部分，我们在427名ASD受试者和190名对照中对SHANK3基因进行了测序。在这里，我们报告了两个假定的致病突变的鉴定：一个是内含子供体剪接位点的从头缺失，一个是来自癫痫父亲的错义遗传。我们能够用从培养的淋巴母细胞中提取的mRNA通过RT-PCR来证实剪接位点缺失的有害影响。错义突变是一种位于68位的亮氨酸，在所有被研究的物种中都是完美保守的，预计会扰乱一个α-螺旋结构域。这些结果进一步支持了SHANK3基因突变在ASD发病机制中的作用。(C)2008年Wiley Liss，Inc.
A number of studies have confirmed that genetic factors play an important role in autism spectrum disorder (ASD). More recently de novo mutations in the SHANK3 gene, a synaptic scaffolding protein, have been associated with the ASD phenotype. As part of our gene discovery strategy, we sequenced the SHANK3 gene in a cohort of 427 ASD subjects and 190 controls. Here, we report the identification of two putative causative mutations: one being a de novo deletion at an intronic donor splice site and one missense transmitted from an epileptic father. We were able to confirm the deleterious effect of the splice site deletion by RT-PCR using mRNA extracted from cultured lymphoblastoid cells. The missense mutation, a leucine to proline at amino acid position 68, is perfectly conserved across all species examined, and would be predicted to disrupt an alpha-helical domain. These results further support the role of SHANK3 gene disruption in the etiology of ASD. (C) 2008 Wiley Liss, Inc.