Abstract：
Background and Objectives: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNVs) and is recommended for the initial genetic testing of patients with autism spectrum disorder (ASD). This study aims to determine the diagnostic yield of array comparative genomic hybridization (array-CGH) in ASD patients from a cohort of Chinese patients in Taiwan. Materials and Methods: Enrolled in this study were 80 ASD children (49 males and 31 females; 2-16 years old) followed up at Taipei MacKay Memorial Hospital between January 2010 and December 2020. The genomic DNA extracted from blood samples was analyzed by array-CGH via the Affymetrix GeneChip Genome-Wide Human single nucleotide polymorphism (SNP) and NimbleGen International Standards for Cytogenomic Arrays (ISCA) Plus Cytogenetic Arrays. The CNVs were classified into five groups: pathogenic (pathologic variant), likely pathogenic (potential pathologic variant), likely benign (potential normal genomic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance), according to the American College of Medical Genetics (ACMG) guidelines. Results: We identified 47 CNVs, 31 of which in 27 patients were clinically significant. The overall diagnostic yield was 33.8%. The most frequently clinically significant CNV was 15q11.2 deletion, which was present in 4 (5.0%) patients. Conclusions: In this study, a satisfactory diagnostic yield of array-CGH was demonstrated in a Taiwanese ASD patient cohort, supporting the clinical usefulness of array-CGH as the first-line testing of ASD in Taiwan.
摘要：
背景与目的：染色体微阵列对亚显微拷贝数变异（CNV）的鉴定具有较高的敏感性，推荐用于自闭症谱系障碍（ASD）患者的初始基因检测。本研究旨在从台湾的一组中国患者中确定阵列比较基因组杂交（array-CGH）在ASD患者中的诊断率。材料与方法：2010年1月至2020年12月在台北麦凯纪念医院随访的80名ASD儿童（男49名，女31名；2-16岁）。通过Affymetrix基因芯片全基因组人类单核苷酸多态性（SNP）和NimbleGen细胞基因组阵列（ISCA）加细胞遗传学阵列国际标准，通过阵列CGH分析了从血液样品中提取的基因组DNA。CNV分为五组：致病性（病理性变异），可能致病（潜在的病理变异），可能是良性的（潜在的正常基因组变异），良性（正常基因组变异），和不确定的临床意义(不确定意义的方差)，根据美国医学遗传学学会（ACMG）指南。结果：我们确定了47个CNVs，其中27例患者中有31例具有临床意义。总诊断率为33.8%。最常见的临床显着CNV是15q11.2缺失，存在于4例（5.0％）患者中。结论：在这项研究中，在台湾ASD患者队列中证明阵列CGH的诊断结果令人满意，支持array-CGH作为台湾ASD一线检测的临床实用性。
