Ann Lab Med 2018; 38(5): 473-480  https://doi.org/10.3343/alm.2018.38.5.473
Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability
Jin Sook Lee, M.D.1*, Hee Hwang, M.D.2*, Soo Yeon Kim, M.D.3, Ki Joong Kim, M.D.3, Jin Sun Choi, M.S.4, Mi Jung Woo, M.S.4, Young Min Choi, M.D.4,5, Jong Kwan Jun, M.D.4,5, Byung Chan Lim, M.D.3,4, and Jong-Hee Chae, M.D.3,4
Department of Pediatrics1, Department of Genome Medicine and Science, Gil Medical Center, Gachon University College of Medicine, Incheon; Department of Pediatrics2, Seoul National University Bundang Hospital, Seongnam; Department of Pediatrics3, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul; The Institute of Reproductive Medicine and Population4, Medical Research Center, Seoul National University College of Medicine, Seoul; Department of Obstetrics and Gynecology5, Seoul National University Hospital, Seoul, Korea
Corresponding author: Byung Chan Lim
https://orcid.org/0000-0002-8509-4135
Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-2364
Fax: +82-2-743-3455
E-mail: prabbit7@snu.ac.kr
*These authors contributed equally to this work as first authors
Received: August 17, 2017; Revised: December 1, 2017; Accepted: May 10, 2018; Published online: September 1, 2018.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea.
Methods: We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Children’s Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR.
Results: We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13.
Conclusions: This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.
Keywords: Chromosomal microarray, Copy number variation, Developmental delay, Intellectual disability, Diagnostic utility



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