Copy Number Variants in Patients with Autism and Additional Clinical Features: Report of VIPR2 Duplication and a Novel Microduplication Syndrome.

Abstract

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.