SUDDEN CARDIAC DEATH IN YOUNG ATHLETES: EXOME SEQUENCING RESULTS

Ranking risks and prevention of sudden cardiac death in professional young athletes is one of the important unresolved problems in sports medicine. Intense physical exertion can lead to adaptive changes in the cardiovascular system, which can mask some inherited diseases with predominant myocardial involvement, such as hypertrophic cardiomyopathy. Undiagnosed cases of such diseases can be a risk factor for fatal outcomes associated with training and competitive activities, making this problem extremely relevant. The aim was to conduct a diagnostic search for possible molecular causes of cardiovascular diseases associated with a high risk of sudden death in young athletes. Methods. Whole-exome sequencing of DNA extracted from two groups of biomaterials was performed: 9 autopsy samples of heart tissues from young athletes who died during intense physical exertion, and 3 samples of venous blood from active athletes of the Russian national teams. The obtained data were subjected to bioinformatic analysis and clinical interpretation. Results. A total of 12 DNA samples were analyzed using a panel of 277 genes associated with the development of cardiovascular diseases with a high risk of sudden death. In 4 out of 12 samples (33.3%), variants likely related to the phenotype were found upon clinical interpretation of the sequencing results. A pathogenic variant was found in the MYBPC3 gene, leading to the development of hypertrophic cardiomyopathy (OMIM: 115197), and a likely pathogenic variant was found in the TRPM4 gene, associated with progressive familial heart block type IB (OMIM: 618531). Two variants with uncertain clinical significance were also found in the CAV3 and SCN1B genes. Conclusion. Currently, data from high-throughput sequencing are being accumulated to search for the molecular basis of cardiovascular diseases with a high risk of sudden cardiac death. Identifying young athletes who are carriers of pathogenic and likely pathogenic gene variants is an effective measure for preventing fatal outcomes and personalizing medical support for professional athletes.