16p13 aberrations predispose to autism and MR

Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array-based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR. This prompted us to search for such genomic imbalances in autism and related disorders. Here we describe a 1.5 Mb duplication on chromosome 16p13.1, found in four autistic male patients from three families and several variably affected and unaffected relatives. A deletion of the same interval was identified in three unrelated patients with MR and other clinical abnormalities. Duplications and deletions of this interval have not been described before, neither as copy number variants in the Database of Genomic Variants nor in >600 individuals from other cohorts examined by high resolution array CGH in our laboratory. Thus, this is the first description of a recurrent genomic imbalance predisposing to autism and/or MR. Keywords: array CGH In this study, we have analysed six index patients and some of their relatives by submegabase resolution array CGH. Experiments were done without dye swap.

自闭症与智力障碍（mental retardation, MR）常存在共病关联，提示二者在病因学上存在相关性。近年来，基于芯片的比较基因组杂交技术（array-based comparative genomic hybridization, array CGH）已证实亚显微缺失与重复是智力障碍的常见致病原因。这一发现促使我们在自闭症及相关障碍患者中探寻此类基因组失衡变异。本研究报道了16号染色体p13.1区域的1.5 Mb重复变异，该变异见于3个家系中的4名自闭症男性患者，以及若干表型各异的受累与未受累亲属。同时，我们在3名无亲缘关系且伴其他临床异常的智力障碍患者中，发现了该区域的缺失变异。截至目前，该区域的重复与缺失变异尚未见报道——既未在基因组变异数据库（Database of Genomic Variants）中作为拷贝数变异被收录，也未在本实验室通过高分辨率array CGH检测的600余名其他队列个体中被发现。因此，本研究首次报道了可增加自闭症和/或智力障碍患病风险的复发性基因组失衡变异。关键词：array CGH。本研究通过亚兆碱基分辨率的array CGH技术，对6名先证者及其部分家属进行了检测，所有实验均未进行染料交换。