1. 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
- Author
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Yonggoo Kim, Ji Yoon Han, Dae Hyun Jang, Jiyeon Kim, Yeonsook Moon, So Young Kim, Eunhee Han, Myungshin Kim, Joonhong Park, Hayoung Choi, Bo Young Hong, Joo Hyun Park, Jung Hyun Lee, Woori Jang, In Kyung Sung, Jung Ok Son, Hyojin Chae, Ahlm Kwon, Sang Jee Lee, and In Goo Lee
- Subjects
0301 basic medicine ,Male ,Pediatrics ,Autism Spectrum Disorder ,Developmental delay ,Duchenne muscular dystrophy ,Developmental Disabilities ,Clinical Biochemistry ,Intellectual disability ,030105 genetics & heredity ,Gene Duplication ,Gene duplication ,Prospective Studies ,Prospective cohort study ,Child ,health care economics and organizations ,Comparative Genomic Hybridization ,General Medicine ,Microdeletion syndrome ,Autism spectrum disorders ,Benign ,Child, Preschool ,Female ,Original Article ,Chromosomal microarray analysis ,Adult ,medicine.medical_specialty ,Down syndrome ,Adolescent ,Karyotype ,Chromosomes ,03 medical and health sciences ,Young Adult ,Republic of Korea ,medicine ,Humans ,Abnormalities, Multiple ,Pathogenic ,business.industry ,Variant of unknown significance ,Clinical management ,Biochemistry (medical) ,Cytogenetics ,Infant, Newborn ,Infant ,medicine.disease ,Chromosome Banding ,030104 developmental biology ,Multiple congenital anomalies ,Autism ,business ,Diagnostic Genetics ,Gene Deletion ,Variant of possible significance - 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.
- Published
- 2018