국내 단일기관 마이크로어레이검사 현황과 임상적 유용성 분석
Current Status and Clinical Utility of Chromosomal Microarray Analysis: A Single-center Study
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초록
목적최근 마이크로어레이검사(chromosomal microarray analysis)는 임상적 사용이 증가하고 있는데, 이는 복제 수변이(copy number variants)가 지적 장애, 발달지연 및 다른 유전체에 의한 이형 특징의 주요원인으로 간주되기 때문이다. 이번 연구는 국내 단일기관에서 이러한 질환을 검출하는데 마이크로어레이검사의 임상 적 유용성을 확인해보고자 하였다. 대상과 방법2019년부터 2022년까지 충북대학교병원에서 마이크로어레이검사가 시행된 141명의 환자를 대상으로 하였 다. 환자들은 증상의 유무에 따라 두 개의 집단으로 구분하였다. 검출된 복제수변이는 미국의학유전학회 (American College of Medical Genetics and Genomics (ACMG) 가이드라인에 따라 분류하였다. 결과총 74개의 복제수변이가 53명의 환자(37.6%)에게서 검출되었다. 병원성 변이 혹은 유사 병원성 변이가 검 출된 경우를 기준으로 진단율은 24.7% (35/141)이었다. 양성변이를 제외한 57개 복제수변이 중 병인성 (pathogenic)은 23개, 유사 병원성 변이는 17개, 불확실성 변이는 17개였다. 결실과 중복 그리고 동형접합 성(homozygosity)는 각각 30, 22, 5개가 검출되었고, 이 들 중 16p13.11 결실이 가장 많았다. 결론마이크로어레이검사의 진단율은 이전 연구와 유사하였다. 마이크로어레이검사는 발달지연, 지적장애, 뇌전 증, 선천기형이 있는 환자들에게 1차적으로 시행할 수 있는 유용한 검사라고 생각한다.
Abstract
Purpose Recently, the clinical use of chromosomal microarray analysis (CMA) has increased because copy number variants (CNVs) are considered major causes of intellectual disability, developmental delay, and other genetic disorders associated with dysmorphic features. This single-center study was conducted to demonstrate the clinical utility of CMA for detecting these diseases. Methods We performed CMA for CNVs in 141 patients at the Chungbuk National University Hospital between 2019 and 2022. Participants were divided into two groups: patients with and without clinical features. CNV results were classified into five categories according to the American College of Medical Genetics and Genomics guidelines. Results A total of 74 CNVs were detected in 53 patients (37.6%). Based on cases in which pathogenic or likely pathogenic variants were detected, the diagnostic yield was 24.7% (35/141). Among these, 57 CNVs, excluding benign/likely benign variants, were classified as pathogenic (n = 23), likely pathogenic (n = 17), or variants of uncertain significance (n = 17). Deletion, duplication, and loss of heterozygosity were detected in 30, 22, and five cases, respectively, with 16p13.11 deletion being the most common. Conclusions The diagnostic yield of CMA was similar to that previously reported. This study suggests that the clinical application of CMA should be recommended as a first-tier test for symptomatic patients.
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