篇名 | Targeted Next Generation Sequencing for Genetic Mutations of Dilated Cardiomyopathy |
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卷期 | 35:6 |
作者 | Jih-Kai Yeh 、 Wei-Hsiu Liu 、 Chao-Yung Wang 、 Jang-Jih Lu 、 Chien-Hsiun Chen 、 Yah-Huei Wu-Chou 、 Pi-Yueh Chang 、 Shih-Cheng Chang 、 Chia-Hung Yang 、 Ming-Lung Tsai 、 Ming-Yun Ho 、 I-Chang Hsieh 、 Ming-Shien Wen |
頁次 | 571-584 |
關鍵字 | Dilated cardiomyopathy 、 Genetic mutation 、 Next generation sequencing 、 MEDLINE 、 Scopus 、 SCIE |
出刊日期 | 201911 |
DOI | 10.6515/ACS.201911_35(6).20190402A |
Background: Approximately one-third of cases of dilated cardiomyopathy (DCM) are caused by geneticmutations. With new sequencing technologies, numerous variants have been associated with this inherited cardiomyopathy, however the prevalence and genotype-phenotype correlations in different ethnic cohorts remain unclear. This study aimed to investigate the variants in Chinese DCM patients and correlate them with clinical presentations and prognosis. Methods and Results: From September 2013 to December 2016, 70 index patients underwent DNA sequencing for 12 common disease-causing genes with next generation sequencing. Using a bioinformatics filtering process, 12 rare truncating variants (7 nonsense variants, 4 frameshift variants, and 1 splice site variant) and 29 rare missense variants were identified. Of these, 3 patients were double heterozygotes and 10 patients were compound heterozygotes. Overall, 47.1% (33/70) of the index patients had the seputatively pathogenic variants. The majority (33/41, 80.4%) of these variants were located in titin (TTN). More than 80% of the TTN variants (27/33, 81.8%) were distributed in the A band region of the sarcomere. Patients carrying these variants did not have a different phenotype in disease severity, clinical outcome and reversibility of ventricular function compared with non-carriers. Conclusions: Several new rare variants were identified in a Chinese population in this study, indicating that there are ethnic differences in genetic mutations in DCM patients. TTN remains the major disease-causing gene. Our results could be a reference for future genetic tests in Chinese populations. No specific genotype-phenotype correlations were found, however a prospective large cohort study may be needed to confirm our findings.