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.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder wherein patients have difficulty in communication and social interactions, stereotypical behaviors, and restricted interests
An autism diagnostic interview-revised (ADI-R) [19] was used to confirm the diagnosis of autism. These patients were diagnosed with idiopathic autism spectrum disorder (ASD), which is of unknown origin, and we excluded other potential etiologies such as neurocutaneous syndromes, other specific syndromes, and congenital or acquired infections among other common causes of autism before they had array-CGH
There were 27 ASD patients (33.8%) in our study with clinically significant copy number variants (CNVs) detected by array-CGH
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder wherein patients have difficulty in communication and social interactions, stereotypical behaviors, and restricted interests. Array comparative genomic hybridization (array-CGH) and single nucleotide polymorphism (SNP) genotyping array, as chromosomal microarray analysis (CMA), are initially performed as cytogenetic diagnostic tests for ASD [3,4]. Before the development of CMA, karyotyping was the standard method to detect genetic anomalies in ASD patients. This could only detect large and microscopically visible chromosomal changes (>5–7 Mb), with a low diagnostic rate (3–5%) [3,5]. Fluorescence in situ hybridization (FISH) is another tool for detecting submicroscopic deletions and duplications It could increase the diagnostic yield by 2% to 3% [3,6,7]. 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
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