| Abstract [eng] |
Numerous studies have been conducted in various countries and ethnic groups to investigate the genetic causes of cardiomyopathies (CM), and the genotype-phenotype relationship, however, the Lithuanian CM population has not yet been studied. The aim of the study was to analyse the genotype-phenotype relationship in individuals with a clinical diagnosis of cardiomyopathy who have undergone molecular genetic and clinical evaluation. A mixed-cohort observational study was conducted at Vilnius University Hospital Santaros Klinikos. The study included more than 300 adult individuals who had been clinically diagnosed with the CM phenotype and underwnt genetic testing. Hypertrophic cardiomyopathy (HCM) was the most frequently identified phenotype in the study cohort. The most common pathogenic/likely pathogenic variants were found in the MYBPC3 and MYH7 genes. Twenty-four novel variants not previously reported in the literature and associated with CM phenotype were identified. During the study, morphological and clinical differences of HCM associated with genotype were observed: pathogenic/likely pathogenic variants were related to an earlier onset of HCM, more pronounced left ventricular hypertrophy, a higher HCM sudden cardiac death risk and earlier adverse events. Molecular and functional characterisation of novel variants (TTR c.302C>T, DNMT3A c.2324C>A) provided a more comprehensive understanding of the disease mechanism and improved patients management. |
