Ann Lab Med.  2015 Sep;35(5):510-518. 10.3343/alm.2015.35.5.510.

Routine Chromosomal Microarray Analysis is Necessary in Korean Patients With Unexplained Developmental Delay/Mental Retardation/Autism Spectrum Disorder

• Shin S
• Yu N
• Choi JR
• Jeong S
• Lee KA

• KMID: 2369767
• DOI: http://doi.org/10.3343/alm.2015.35.5.510

Abstract

BACKGROUND
All over the world, chromosomal microarray (CMA) is now the first tier diagnostic assay for genetic testing to evaluate developmental delay (DD), mental retardation (MR), and autism spectrum disorder (ASD) with unknown etiology. The average diagnostic yield of the CMA test is known to be about 12.2%, while that of conventional G-banding karyotype is below 3%. This study aimed to assess the usefulness of CMA for the purpose of clinical diagnostic testing in the Korean population.
METHODS
We performed CMA and multiplex ligation-dependent probe amplification (MLPA) tests in 96 patients with normal karyotype and unexplained DD, MR, or ASD. The CMA was conducted with CytoScan 750K array (Affymetrix, USA) with an average resolution of 100 kb.
RESULTS
Pathogenic copy number variations (CNVs) were detected in 15 patients by CMA and in two patients by MLPA for four known microdeletion syndromes (Prader-Willi/Angelman syndrome, DiGeorge syndrome, Miller-Dieker syndrome and Williams syndrome) designated by National Health Insurance system in Korea. The diagnostic yield was 15.6% and 2.1%, respectively. Thirteen (13.5%) patients (excluding cases with pathogenic CNVs) had variants of uncertain clinical significance. There was one patient with a 17.1-megabase (Mb) region of homozygosity on chromosome 4q.
CONCLUSIONS
Our findings suggest the necessity of CMA as a routine diagnostic test for unexplained DD, MR, and ASD in Korea.

Keyword

Copy number variation; Chromosomal microarray; Developmental delay; Mental retardation; Autism spectrum disorders

MeSH Terms

Child
Child Development Disorders, Pervasive
Classical Lissencephalies and Subcortical Band Heterotopias
Diagnostic Tests, Routine
DiGeorge Syndrome
Genetic Testing
Humans
Intellectual Disability
Karyotype
Korea
Microarray Analysis*
Multiplex Polymerase Chain Reaction
National Health Programs

Figure

• 

  Fig. 1 Multiplex ligation-dependent probe amplification (MLPA) and microarray results of patient with Cri du Chat syndrome. (A) The MLPA scatter plot showing deletion of a probe site on TERT. (B) Microarray profile with a copy number loss on 5p15.33p15.31 (113,576-7,183,668) (red bar).

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