국내 발달지연과 정신지체 환자에 대한 우선적 검사로서 염색체 마이크로에레이의 임상적 적용에 대한 연구
Clinical application of chromosomal microarray as a first-tier chromosome aberration test for patients with developmental delay and intellectual disability in Korea
- 주제(키워드) chromosomal microarray (CMA) , copy-number variations (CNVs) , congenital anomaly , developmental delay (DD) , intellectual disability (ID)
- 발행기관 아주대학교
- 지도교수 김현주, 정선용
- 발행년도 2017
- 학위수여년월 2017. 2
- 학위명 석사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000024829
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Background: Chromosomal microarray (CMA) is a cytogenetic diagnostic test for chromosomal abnormalities in many diseases, which can provide the fast and accurate detection of copy-number variations (CNVs). International guidelines recommend specific approaches for the use of CMA as a first-tier clinical diagnostic test for patients with developmental disabilities or congenital anomalies. However, CMA is not used as a general diagnostic test in Korea because Korea’s insurance laws do not allow the use of CMA as a clinical diagnostic method. In this study, I aimed to investigate the clinical utility and limitations of CMA as a first-tier chromosome aberration test for patients with developmental delay (DD), intellectual disability (ID), and autism spectrum disorders (ASD) in Korea. Methods: Eighty-seven patients with neurodevelopmental disorders (16 ID, 70 DD and one ASD) and 32 patients with both congenital anomalies and symptoms of ID or DD revealed normal conventional G-banded karyotypes and were therefore referred by a clinical geneticist for further chromosomal analysis from December 2012 to July 2016. CMA was performed in a single clinical laboratory on a total of 182 samples from 119 patients and 63 family members of 37 patients. The clinical significance of CNVs and clinical features of patients and family members were studied. Results: The CMA results of 119 patients revealed 36 pathogenic CNVs (30.3%), 11 CNVs of variants of uncertain clinical significance (VOUS) (7.6%), 24 benign CNVs (17.6%), and no abnormalities in 53 patients (44.5%). Among the 63 family members of 37 patients, the CMA results revealed five pathogenic CNVs (8%), five VOUS (8%), 12 benign CNVs (19%), and no abnormalities in 41 cases (65%). In the 11 family members with abnormal phenotypes, the CMA results revealed five pathogenic CNVs (45.5%), two VOUS (18.2%), one benign CNV (9.1%), and three normal results (27.3%). The detection rate for pathogenic CNVs was 30.3% (36/119), which is higher than the average detection rate of previous reports. Conclusions: In this study, pathogenic CNVs were detected in 36 patients (30.3%) and it was demonstrated that CMA is a very powerful tool with clinical diagnostic utility for patients with DD, ID, ASD, and congenital anomalies. However, there was a limitation of CMA results with VOUS for interpretation for nine patients (7.6%). The significance of VOUS can be improved by further testing through a familial studies and exome sequencing.
more목차
Abstract i
Table of Contents iii
List of Figures iv
List of Tables iv
I.Introduction 1
II.Method
A.Patients 3
B.CMA and analysis of chromosomal aberrations 4
III.Result
A.CMA of patients 6
1.Pathogenic CNVs in neurodevelopmetal disorder
patients 7
2.Pathogenic CNVs in congenital anomaly patients 11
B.CMA of patients’ family members 12
C.Chromosomal distribution of pathogenic CNVs 15
IV.Discussion 16
References 22
국문요약 27
목차
List of Figures
Figure 1. Flow diagram of CMA test with patients and patients’ familymembers 3
Figure 2. Distribution of pathogenic CNVs onchromosomes 15
목차
List of Tables
Table 1. The results of CMA patients 6
Table 2. Summary of pathogenic CNVs data for patients 8
Table 3. The results of CMA in patients’ family members 13
Table 4. Comparison of CMA and chromosomal genetic tests 14
Table 5. Comparison of CMA within family group and chromosomal genetic tests 17
Table 6. Comparison of recent chromosomal microarray detection rate in korea 18
