Abstract 4118425: Prevalence and Spectrum of Pathogenic Genetic Variants in Korean Cardiomyopathy Patients: Insights from Next-Generation Sequencing

Background and Aim: Next-generation sequencing (NGS) is increasingly used to identify genetic variants associated with cardiomyopathies, which can aid in precise diagnosis and management. This study aimed to elucidate the prevalence and spectrum of pathogenic and likely pathogenic genetic variants in a cohort of Korean population diagnosed with different forms of cardiomyopathy. Methods: This retrospective study analyzed 122 patients diagnosed with cardiomyopathy at three tertiary hospitals in Korea, all of whom underwent NGS to identify genetic variants between December 2017 and October 2023. Detailed patient records, including clinical diagnoses, imaging results, and family histories, were reviewed to correlate genetic findings with phenotypic data. Results: Of the patients, 35 (28.7%) were found to have pathogenic or likely pathogenic variants, and 43 (35.2%) were found to have only variants of uncertain significance. Of the patients with pathogenic or likely pathogenic variants, 16 had hypertrophic cardiomyopathy (HCM) and 16 had dilated cardiomyopathy (DCM), while 3 remained with an uncertain clinical phenotype. In the HCM group, 16 patients exhibited variants predominantly in MYBPC3 (62.5%), followed by MYH7 (12.5%), and others such as TPM1, TNNI3, PRKAG2, and SCN5A (each 6.3%). Additionally, 43.8% of the HCM group had a familial history of sudden cardiac death or cardiomyopathy, with a mean left ventricular mass index (LVMi) of 148.3 ± 70.4 g/m2 and a mean maximal wall thickness of 17.7 ± 3.9 mm. The DCM group showed a different pattern, with TTN variants in 43.8%, LMNA in 18.8%, and others including MYBPC3, RBM20, TTN2, and KCNQ1 (each 6.3%). This group had a mean left ventricular ejection fraction (LVEF) of 27% and a LVMi of 119.7 g/m2. Conclusion: Our findings highlight significant genetic diversity in cardiomyopathies among Korean patients, with distinct genetic backgrounds observed in HCM and DCM. The high prevalence of specific mutations such as MYBPC3 in HCM and TTN in DCM could guide targeted genetic testing and personalized treatment strategies in these populations.