Ann Lab Med.  2018 Sep;38(5):473-480. 10.3343/alm.2018.38.5.473.

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

• Lee JS
• Hwang H
• Kim SY
• Kim KJ
• Choi JS
• Woo MJ
• Choi YM
• Jun JK
• Lim BC
• Chae JH

• KMID: 2434738
• DOI: http://doi.org/10.3343/alm.2018.38.5.473

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.

Keyword

Chromosomal microarray; Copy number variation; Developmental delay; Intellectual disability; Diagnostic utility

MeSH Terms

Autistic Disorder
Child*
Cohort Studies
Diagnosis
Diagnostic Tests, Routine
Genetic Counseling
Humans
Intellectual Disability*
Korea
Medical Records
Microarray Analysis
Parents
Polymerase Chain Reaction
Retrospective Studies
Seoul
Virulence

Figure

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  Fig. 1 Chromosomal distribution of pathogenic CNVs identified in the present study.Abbreviation: CNV, copy number variation.

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  Fig. 2 Microarray data of the rarely reported pathogenic copy number variations verified in this study: Agilent Human Genome oligonucleotide CGH showing deletions of 2.98 Mb on 2p21p16.3 (A), 1.46 Mb on 3p21.31 (B), 4.22 Mb on 10p11.22p11.21 (C), and 3.3 Mb on 14q24.2 (D).

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