Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability

• Published in: Annals of laboratory medicine Vol. 38; no. 5; pp. 473 - 480
• Main Authors: Lee, Jin Sook, Hwang, Hee, Kim, Soo Yeon, Kim, Ki Joong, Choi, Jin Sun, Woo, Mi Jung, Choi, Young Min, Jun, Jong Kwan, Lim, Byung Chan, Chae, Jong Hee
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Laboratory Medicine 01.09.2018; 대한진단검사의학회
• Subjects: Adolescent; Adult; Child; Child, Preschool; Chromosomes - genetics; Chromosomes - metabolism; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; DNA Copy Number Variations; Female; Gene Duplication; Humans; In Situ Hybridization, Fluorescence; Infant; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Karyotyping; Male; Oligonucleotide Array Sequence Analysis; Original; Real-Time Polymerase Chain Reaction; Retrospective Studies; Sequence Deletion; Young Adult; 병리학; Chromosomal microarray; Copy number variation; Intellectual disability; Developmental delay; Diagnostic utility
• ISSN: 2234-3806; 2234-3814; 2234-3814
• DOI: 10.3343/alm.2018.38.5.473

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. 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. 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. 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.