Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea

• Published in: Annals of laboratory medicine Vol. 39; no. 3; pp. 299 - 310
• Main Authors: Jang, Woori, Kim, Yonggoo, Han, Eunhee, Park, Joonhong, Chae, Hyojin, Kwon, Ahlm, Choi, Hayoung, Kim, Jiyeon, Son, Jung-Ok, Lee, Sang-Jee, Hong, Bo Young, Jang, Dae-Hyun, Han, Ji Yoon, Lee, Jung Hyun, Kim, So Young, Lee, In Goo, Sung, In Kyung, Moon, Yeonsook, Kim, Myungshin, Park, Joo Hyun
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Laboratory Medicine 01.05.2019; 대한진단검사의학회
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Adolescent; Adult; Autism Spectrum Disorder - diagnosis; Autism Spectrum Disorder - genetics; Child; Child, Preschool; Chromosome Banding - methods; Chromosomes - genetics; Comparative Genomic Hybridization; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; Female; Gene Deletion; Gene Duplication; Humans; Infant; Infant, Newborn; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Karyotype; Male; Original; Prospective Studies; Republic of Korea; Young Adult; 병리학; Republic of Korea; Autism spectrum disorders; Multiple congenital anomalies; Clinical management; Intellectual disability; Pathogenic; Benign; Chromosomal microarray analysis; Variant of possible significance; Developmental delay; Variant of unknown significance
• ISSN: 2234-3806; 2234-3814; 2234-3814
• DOI: 10.3343/alm.2019.39.3.299

To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: deletion, duplication, and deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.