Targeted next-generation sequencing in Slovak cardiomyopathy patients

Abstract

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.