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KMID : 1100720190390030299
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Annals of Laboratory Medicine
2019 Volume.39 No. 3 p.299 ~ p.310
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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
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Jang Woo-Ri
Kim Yong-Goo
Han Eun-Hee
Park Joon-Hong
Chae Hyo-Jin
Kwon Ahlm
Choi Ha-Young
Kim Ji-Yeon
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 Yeon-Sook
Kim Myung-Shin
Park Joo-Hyun
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Abstract
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Background: 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).
Methods: 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.
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: IMMP2L deletion, PTCH1 duplication, and ATRNL1 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.
Conclusions; 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.
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KEYWORD
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Chromosomal microarray analysis, Pathogenic, Variant of possible significance, Variant of unknown significance, Benign, Clinical management, Developmental delay, Intellectual disability, Autism spectrum disorders, Multiple congenital anomalies
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