Affymetrix CytoScan HD for autism spectrum disorder in children. 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. Overall design: 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.

自闭症谱系障碍（Autism spectrum disorder, ASD）是一类具有显著遗传背景的复杂异质性发育疾病，其发病常由罕见拷贝数变异（copy number variants, CNV）引发。本研究旨在纳入确诊ASD的研究队列，筛选新的ASD候选基因。我们采用染色体微阵列分析（chromosomal microarray analysis, CMA）——即美国加利福尼亚州圣克拉拉Affymetrix公司生产的Cytoscan HD芯片——对87名ASD患者及其亲属的拷贝数变异进行检测，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。本次研究共发现89个罕见CNV：其中8个为致病性变异，12个归类为意义不明确变异（Variant of Uncertain Significance, VOUS）-可能致病性，12个为VOUS-意义不确定，57个为VOUS-可能良性或良性变异。在多名患者中观察到重叠同一基因的致病性/VOUS-可能致病性/VOUS-意义不确定CNV，涉及DOCK8基因与PARK2基因。本研究为PARK2与DOCK8在ASD病因学中的潜在作用提供了新证据，并提示CTNNA2可作为ASD风险的候选基因。
总体实验设计：按照制造商的操作指南，对从外周血样本中提取的DNA开展Affymetrix CytoScan HD芯片检测；针对87名ASD患者及其亲属的Affymetrix CytoScan HD芯片数据进行拷贝数分析。