Affymetrix CytoScan HD for autism spectrum disorder in children

Autism spectrum disorder (ASD) is a complex heterogeneous developmental disease with a significant genetic background that is frequently caused by rare copy number variants (CNV). The aim of the study was to identify new candidate genes for ASD in the studied cohort of ASD-diagnosed patients. We used chromosomal microarray analysis (CMA) - a Cytoscan HD (Affymetrix, Santa Clara, CA, USA) to detect CNV in 87 ASD patients and their relatives and evaluated their clinical significance. Pathogenic and likely pathogenic mutations were identified by CMA in 8 and 9 ASD patients, respectively. CMA revealed 89 rare CNV: 8 pathogenic, 12 designated VOUS - likely pathogenic, 12 VOUS - uncertain, and 57 VOUS - likely benign or benign. CNV (pathogenic/VOUS-likely pathogenic/VOUS - uncertain) overlapping the same gene in more than one patient were observed in DOCK8 gene and PARK2 gene. This work presents new evidence about the possible roles of PARK2 and DOCK8 in the etiology of ASD, and suggests CTNNA2 as a candidate gene for ASD risk. Affymetrix CytoScan HD arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. Copy number analysis of Affymetrix CytoScan HD arrays was performed for 87 ASD patients and their relatives.

孤独症谱系障碍（Autism spectrum disorder, ASD）是一类具有显著遗传背景的复杂异质性发育性疾病，其发病常与稀有拷贝数变异（copy number variants, CNV）相关。本研究旨在纳入经确诊的ASD患者队列，从中筛选出ASD新型候选致病基因。我们采用染色体微阵列分析（chromosomal microarray analysis, CMA）技术，使用Affymetrix Cytoscan HD芯片（美国加利福尼亚州圣克拉拉市Affymetrix公司出品）对87名ASD患者及其亲属的样本进行CNV检测，并评估其临床意义。经CMA检测，分别在8名和9名ASD患者中检出致病性变异与可能致病性变异。本次研究共检出89种稀有CNV，其中8种为致病性变异，12种归类为可能致病性意义未明变异（variant of uncertain significance, VOUS），12种为意义未明变异（VOUS），剩余57种则为可能良性或良性变异。在多名患者中，均观察到覆盖同一基因且属于致病性/可能致病性VOUS/意义未明VOUS类别的CNV，涉及DOCK8与PARK2两个基因。本研究为PARK2与DOCK8在ASD发病机制中的潜在作用提供了新的实验证据，并提示CTNNA2可作为ASD患病风险的候选基因。本研究按照制造商提供的实验操作指南，对从外周血样本中提取的基因组DNA进行了Affymetrix Cytoscan HD芯片检测。随后对87名ASD患者及其亲属的Affymetrix Cytoscan HD芯片结果开展了拷贝数变异分析。