Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
Mol Neurobiol. 2017 Nov;54(9):7019-7027. doi: 10.1007/s12035-016-0202-y. Epub 2016 Oct 28.
Autism is a common neurodevelopmental disorder estimated to affect 1 in 68 children. Many studies have shown the role of copy number variants (CNVs) as a major contributor in the etiology of autism with the overall detection rate of about 10-15 % and over 20 % when syndromic forms of autism exist. In this study, we used array CGH to identify CNVs in 15 Iranian patients with autism. To elevate our diagnostic yield, we selected the sporadic patients who had additional clinical features including intellectual disability (ID), craniofacial anomaly, and seizure. Six out of 15 patients showed clinically relevant CNVs including pathogenic and likely pathogenic copy number gains or losses. We report a novel gene duplication syndrome (10q21.2q21.3 microduplication) and present a new evidence for VIPR2 duplication, as a candidate gene for autism. Furthermore, we describe the first manifesting carrier female with deletion of SLC6A8 and BCAP31 genes on Xq28. Our findings suggest that there might be a higher prevalence of clinically significant CNVs in patients with autism and additional clinical manifestations. The CNV analysis in such patients could lead to the discovery of novel syndromes as well as unraveling the etiology of autism.
自闭症是一种常见的神经发育障碍，估计影响 1/68 的儿童。许多研究表明，拷贝数变异（CNVs）是自闭症发病机制的主要因素，总体检出率约为 10-15%，当存在自闭症综合征形式时，检出率超过 20%。在这项研究中，我们使用阵列 CGH 来鉴定 15 名伊朗自闭症患者的 CNVs。为了提高我们的诊断率，我们选择了具有额外临床特征的散发性患者，包括智力障碍（ID）、颅面异常和癫痫。15 名患者中有 6 名显示出具有临床意义的 CNVs，包括致病性和可能致病性的拷贝数增益或缺失。我们报告了一种新的基因重复综合征（10q21.2q21.3 微重复），并提供了 VIPR2 重复作为自闭症候选基因的新证据。此外，我们描述了携带 SLC6A8 和 BCAP31 基因缺失的 Xq28 上的第一个表现型携带者女性。我们的发现表明，自闭症和其他临床表现的患者中可能存在更高比例的具有临床意义的 CNVs。对这些患者的 CNV 分析可能会发现新的综合征，并揭示自闭症的病因。
