• Woori Jang, Yonggoo Kim, Eunhee Han, Joonhong Park, Hyojin Chae, Ahlm Kwon, Hayoung Choi, Jiyeon Kim, Jung Ok Son, Sang Jee Lee, Bo Young Hong, Dae Hyun Jang, Ji Yoon Han, Jung Hyun Lee, So Young Kim, In Goo Lee, In Kyung Sung, Yeonsook Moon, Myungshin Kim, and Joo Hyun Park.
• Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
• Ann Lab Med. 2019 May 1; 39 (3): 299-310.

BackgroundTo 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).MethodsWe 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.ResultsA 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.ConclusionsClinical 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.© The Korean Society for Laboratory Medicine.

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