Investigation of 25bp deletion-associated frameshift mutation in cardiac myosin-binding protein C gene and potential cardiomyopathy risks among Indian athletes

Background: Hypertrophic cardiomyopathy (HCM) is one of the leading congenital causes of sudden cardiac death/sudden cardiac arrest (SCD/SCA) among young competitive athletes. HCM is genetically inherited in an autosomal dominant manner, and genetic mutations in any one of the 12 myocardial contractile filament protein-encoding genes may be attributed to this heterogeneous disorder. Aims and Objectives: Therefore, our objective was to investigate the prevalence of the MYBPC3 d25bp variant among the athletic population in India, and the presence of HCM-associated pathological left ventricular hypertrophy (LVH) among the MYBPC3 d25bp genotype carrier athletes. Materials and Methods: Oral mouthwash samples were collected from a total of 149 elite athletes (age range: 18–36 years) and screened for MYBPC3 d25bp genotype. We performed resting and cardiac stress 12-channel electrocardiography and echocardiography evaluation on heterozygous MYBPC3 d25bp carrier athletes for HCM phenotype diagnosis. Results: We found 4.7% (7/149; 4 male and 3 female) prevalence of deleterious MYBPC3 d25bp heterozygous genotype among our sample athletes. Based on left ventricular mass index (LVMI) and relative wall thickness (RWT), we observed a mild form of concentric LVH among male (LVMI: 127.2 g/m 2 ; RWT: 0.59) and female (LVMI: 98.1 g/m 2 ; RWT: 0.52) carrier athletes. Conclusion: Based on these results, we recommend long-term clinical follow-ups for athletes carrying MYBPC3 d25bp heterozygous genotype coupled with concentric LVH, during their training and competition to differentiate between physiological training-associated cardiac adaptations and pathological left ventricular parameters and mitigate the potential risk of SCD/SCA. Furthermore, preparticipation screening for HCM and other cardiac anomalies should include genetic testing as well.