GENETIC BASIS FOR CARDIOMYOPATHY IN A REPRESENTATIVE COHORT IN THE CZECH REPUBLIC

Aim: Inherited cardiomyopathies are an important cause of heart failure in patients < 50 years. Our study aims to assess the genetic basis of inherited forms of cardiac failure in the Czech population. Thanks to a shared database and communication we intend to increase the quality and reliability of molecular genetic analysis.

Sample and methodology: The cardiogenetic group within the Czech Genetic Society (SLG ČSL JEP) initiated a shared pseudoanonymized cardiogenetic DNA variant database project. Six accredited diagnostic molecular genetic laboratories perform cardiogenetic studies using next-generation sequencing approaches. 99 genes were analysed in all patients irrespective of the method used in a particular laboratory.

Results: Pseudoanonymized data of 3578 patients (2392 males/1186 females) with cardiomyopathies (CMP): HCM (1585), (DCM (1344), ACM (316), LVNC (122), RCM (27), and uncategorized CMP (184) were until now collected. ACMG.net class 4 and 5 variants were identified in 29 % cases. The most frequently identified genes harbouring the pathogenic DNA variant are MYBPC3 (25 %), TTN (24 %), MYH7 (14 %), and PKP2 (5 %). Most found variants are unique to the probands, but MYBPC3 gene harbours several frequently identified variants in our population.

Conclusion: We show data from the very first national registry of genetic causes of cardiomyopathies in the Czech Republic. Affected individuals are predominantly males. The genetic yield does not significantly differ from the reported ones in other national registries, but the genetic architecture differs from other reported cohorts and could show the special properties of our genetic background. Further analysis may allow us to identify population-specific pathogenic variants, and the inter-laboratory communication contributes to better quality of genetic service.

Grants: LX22NPO5104