Molecular Diagnosis of Hereditary Spherocytosis by Multi-gene Target Sequencing in Korea : 다중 유전자 타깃 염기서열분석법을 이용한 한국인 유전구형적혈구증 환자의 분자진단

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의과대학 임상의과학과
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서울대학교 대학원
Hereditary spherocytosisNext generation sequencingRBC membrane protein gene
학위논문 (박사)-- 서울대학교 대학원 : 의과대학 임상의과학과, 2016. 2. 이동순.
Background: Hereditary spherocytosis (HS) is the most common cause of hereditary hemolytic anemia in Europe and North America. Current tests used to diagnose HS focus on the detection of hemolysis or indirectly assess protein defects. Direct methods to detect protein defects are complicated and difficult to implement. Recent next-generation sequencing (NGS) methods enable large-scale gene mutation analyses to be used for such diagnoses. In this study, we investigated the patterns of genetic variation associated with HS to determine the molecular mechanisms underlying the condition. Specifically, we analyzed mutations in red blood cell membrane protein-encoding genes and enzyme-encoding genes in Korean HS patients using NGS.
Methods: In total, 61 patients with HS were enrolled in this study. Targeted sequencing of 43 genes (17 membrane protein-encoding genes, 20 enzyme-encoding genes, and 6 additional candidate genes) was performed using the Illumina HiSeq platform and variants were called according to a data-processing pipeline.
Results: Of the 61 patients, 50 (82%) had one or more significant variants in a membrane protein gene. A total of 54 significant variants (8 previously reported and 46 novel) were detected in 6 membrane protein-encoding genes, i.e., SPTB, ANK1, SPTA1, SLC4A1, EPB41, and EPB42. The most variants (28) were detected in SPTB. Four significant variants, all of which were previously reported, were detected in genes encoding enzymes (ALDOB, G6PD, GAPDH, and GSR). Additionally, 5 previously reported variants were detected in UGT1A1. These results suggest 35 primer sets that can be used to diagnose HS.
Conclusions: This was the first large-scaled genetic study of Korean HS patients. These results clarify the pattern of genetic variation associated with HS in Korean patients. They will enable easier, more rapid diagnosis of HS.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Clinical Medical Sciences (임상의과학과)Theses (Ph.D. / Sc.D._임상의과학과)
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