Targeted Next Generation Sequencing for Genetic Mutations of Dilated Cardiomyopathy.

Autor:	Yeh JK; Department of Cardiology., Liu WH; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital., Wang CY; Department of Cardiology.; College of Medicine, Chang Gung University, Taoyuan., Lu JJ; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital.; College of Medicine, Chang Gung University, Taoyuan., Chen CH; Institute of Biomedical Sciences, Academia Sinica, Taipei., Wu-Chou YH; Department of Medical Research, Linkou Chang Gung Memorial Hospital and Graduate of Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan., Chang PY; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital., Chang SC; Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital., Yang CH; Department of Cardiology., Tsai ML; Department of Cardiology., Ho MY; Department of Cardiology., Hsieh IC; Department of Cardiology.; College of Medicine, Chang Gung University, Taoyuan., Wen MS; Department of Cardiology.; College of Medicine, Chang Gung University, Taoyuan.
Jazyk:	angličtina
Zdroj:	Acta Cardiologica Sinica [Acta Cardiol Sin] 2019 Nov; Vol. 35 (6), pp. 571-584.
DOI:	10.6515/ACS.201911_35(6).20190402A
Abstrakt:	Background: Approximately one-third of cases of dilated cardiomyopathy (DCM) are caused by genetic mutations. 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.
Databáze:	MEDLINE
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