Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome
Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome
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DOI：
10.1007/s12035-016-0202-y
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发表时间：
2017-11-01
影响因子：
5.1
通讯作者：
Behjati, Farkhondeh
中科院分区：
文献类型：
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作者：
Firouzabadi, Saghar Ghasemi;Kariminejad, Roxana;Behjati, Farkhondeh
自闭症是一种常见的神经发育障碍，估计每 68 名儿童中就有 1 人患有自闭症。许多研究表明，拷贝数变异 (CNV) 在自闭症病因学中发挥着重要作用，总体检出率约为 10-15%，当存在综合症形式的自闭症时，检出率超过 20%。在这项研究中，我们使用阵列 CGH 来识别 15 名伊朗自闭症患者的 CNV。为了提高诊断率，我们选择了具有其他临床特征的零星患者，包括智力障碍 (ID)、颅面异常和癫痫发作。 15 名患者中有 6 名表现出临床相关的 CNV，包括致病性和可能致病性拷贝数的增加或减少。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，我们描述了第一个在 Xq28 上缺失 SLC6A8 和 BCAP31 基因的女性携带者。我们的研究结果表明，自闭症和其他临床表现患者中具有临床意义的 CNV 的患病率可能更高。对此类患者进行 CNV 分析可能会发现新的综合征并揭示自闭症的病因。
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.