Targeted next-generation sequencing in Slovak cardiomyopathy patients

Bratislava Medical Journal

article

E. Nagyova¹  J. Radvanszky⁴  M. Hyblova¹  V. Simovicova⁶  E. Goncalvesova⁶  F. W. Asselbergs²  L. Kadasi¹  T. Szemes¹  G. Minarik¹ 

[1] Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava;Department of Cardiology, Division Heart & Lungs, UMC Utrecht, University of Utrecht;Medirex Inc.;Geneton Ltd.;Institute for Clinical and Translational Research, Biomedical Research Centre, Slovak Academy of Sciences;Heart Failure and Transplant Department, National Cardiovascular Institute;Durrer Center for Cardiovascular Research, Netherlands Heart Institute;Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London

关键词: cardiomyopathy;    Slovak patients;    next-generation sequencing;    gene panel;    genetic testing;   

DOI  :  10.4149/BLL_2019_007

学科分类：医学（综合）

来源: AEPress, s.r.o.

【 摘 要 】

OBJECTIVES: For the first time we used targeted next-generation sequencing to detect candidate pathogenic variants in Slovak cardiomyopathy patients. BACKGROUND: Targeted next-generation sequencing is considered to be the best practice in genetic diagnostics of cardiomyopathies. However, in Slovakia, with high cardiomyopathies prevalence of 1/440, the current diagnostic tests are still based on Sanger sequencing of a few genes. Consequently, little is known about the exact contribution of pathogenic variants in known cardiomyopathy genes in Slovak patients. METHODS: We used a panel of 46 known cardiomyopathy-associated genes to detect genetic variants in 16 Slovak cardiomyopathy patients (6 dilated, 8 hypertrophic, 2 non-compaction subtypes). RESULTS: We identified candidate pathogenic variants in 11 of 16 patients (69 %). Genes with higher count of candidate pathogenic variants were MYBPC3, MYH and TTN, each with 3 different variants. Seven variants ACTC1 (c.329C>T), ANKRD1 (c.683G>T), MYH7 (c.1025C>T), PKP2 (c.2003delA), TTN (c.51655C>T, c.84841G>T, c.101874_101881delAGAATTTG) have been detected for the first time and might represent Slovak-specific genetic cause. CONCLUSIONS: We have performed genetic testing of previously untested Slovak cardiomyopathy patients using next-generation sequencing cardiomyopathy gene panel. Given the high percentage of candidate pathogenic variants it should be recommended to implement this method into routine genetic diagnostic practice in Slovakia (Tab. 4, Ref. 39).

【 授权许可】

CC BY