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Acta Cardiologica Sinica MEDLINESCIEScopus

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篇名 Targeted Next Generation Sequencing for Genetic Mutations of Dilated Cardiomyopathy
卷期 35:6
作者 Jih-Kai YehWei-Hsiu LiuChao-Yung WangJang-Jih LuChien-Hsiun ChenYah-Huei Wu-ChouPi-Yueh ChangShih-Cheng ChangChia-Hung YangMing-Lung TsaiMing-Yun HoI-Chang HsiehMing-Shien Wen
頁次 571-584
關鍵字 Dilated cardiomyopathyGenetic mutationNext generation sequencingMEDLINEScopusSCIE
出刊日期 201911
DOI 10.6515/ACS.201911_35(6).20190402A

中文摘要

英文摘要

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.

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