Chromosomal Microarray Analysis as a First-Tier Clinical Diagnostic Test in Patients With Developmental Delay/Intellectual Disability, Autism Spectrum Disorders, and Multiple Congenital Anomalies: A Prospective Multicenter Study in Korea
10.3343/alm.2019.39.3.299
- Author:
Woori JANG
1
;
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
;
Joo Hyun PARK
Author Information
1. Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. microkim@catholic.ac.kr
- Publication Type:Multicenter Study
- Keywords:
Chromosomal microarray analysis;
Pathogenic;
Variant of possible significance;
Variant of unknown significance;
Benign;
Clinical management;
Developmental delay;
Intellectual disability;
Autism spectrum disorders;
Multiple congenital anomalies
- MeSH:
Autism Spectrum Disorder;
Autistic Disorder;
Cytogenetics;
Diagnostic Tests, Routine;
Down Syndrome;
Humans;
Intellectual Disability;
Korea;
Microarray Analysis;
Muscular Dystrophy, Duchenne;
Prader-Willi Syndrome;
Prospective Studies;
Referral and Consultation;
Specialization
- From:Annals of Laboratory Medicine
2019;39(3):299-310
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: To 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). METHODS: We 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. RESULTS: A 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. CONCLUSIONS: Clinical 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.
