Department of Child and Adolescent Psychiatry, University Medical Centre, Utrecht, The Netherlands.
Clin Genet. 2009 Oct;76(4):348-56. doi: 10.1111/j.1399-0004.2009.01254.x.
Autism spectrum disorder (ASD) represents a set of neurodevelopmental disorders with a strong genetic aetiology. Chromosomal rearrangements have been detected in 5-10% of the patients with ASD, and recent applications of array comparative genomic hybridisation (aCGH) are identifying further candidate regions and genes. In this study, we present four patients who implicate microcephalin 1 (MCPH1) in band 8p23.1 as an ASD susceptibility gene. Patient 1 was a girl with a syndromic form of autistic disorder satisfying the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS) and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Oligonucleotide aCGH (oaCGH) showed that she had a classic inv dup del(8)(qter-> p23.1::p23.1-> p21.2) containing at least three candidate genes; MCPH1 and DLGAP2 within the 6.9-Mb terminal deletion and NEF3 within the concomitant 14.1-Mb duplication. Three further patients with MCPH1 copy number changes were found using single-nucleotide polymorphism (SNP) array analysis in a cohort of 54 families with ASD patients. Our results show that ASD can be a component of the classical inv dup del(8) phenotype and identify changes in copy number of MCPH1 as a susceptibility factor for ASD in the distal short arm of chromosome 8.
自闭症谱系障碍 (ASD) 代表一组具有强烈遗传病因的神经发育障碍。在 5-10%的 ASD 患者中已经检测到染色体重排，最近应用的比较基因组杂交(array comparative genomic hybridisation, aCGH) 正在鉴定更多的候选区域和基因。在这项研究中，我们介绍了四名患者，他们提示微脑畸形蛋白 1 (MCPH1) 在 8p23.1 带中与 ASD 易感性相关。患者 1 是一名女孩，患有满足自闭症诊断访谈修订版 (Autism Diagnostic Interview-Revised, ADI-R)、自闭症诊断观察量表 (Autism Diagnostic Observation Schedule, ADOS) 和精神障碍诊断与统计手册 (Diagnostic and Statistical Manual of Mental Disorders, DSM-IV) 标准的综合征形式的自闭症障碍。寡核苷酸 aCGH (oocyte array comparative genomic hybridisation, oaCGH) 显示她具有经典的 inv dup del(8)(qter-> p23.1::p23.1-> p21.2)，其中包含至少三个候选基因；MCPH1 和 DLGAP2 在 6.9-Mb 末端缺失，NEF3 在伴随的 14.1-Mb 重复。使用 SNP 芯片分析在一组 54 个 ASD 患者的家庭中发现了另外 3 名 MCPH1 拷贝数变化的患者。我们的结果表明，ASD 可能是经典 inv dup del(8)表型的一部分，并确定 MCPH1 拷贝数的变化是 8 号染色体短臂远端 ASD 的易感因素。
