CONTRIBUTION OF SARCOMERIC GENE VARIANTS TO THE PREDICTION OF SUDDEN CARDIAC DEATH RISK IN FAMILIAL HYPERTROPHIC CARDIOMYOPATHY

Abstract

Objective: Hypertrophic cardiomyopathy (HCM) is one of sudden cardiac death (SCD) causes. This study aimed to identify high-risk pathogenic variants for SCD in the three sarcomeric genes with the most frequent mutations in HCM. Material and Method: The study included 12 adult HCM index cases with a family history of SCD and/or HCM, and 31 of their family members. All the participants were evaluated with detailed cardiac examinations. The exonic regions of the MYH7, MYBPC3 and TNNT2 genes were analysed using CorTAG HCM1 resequencing arrays. Results: Six pathogenic variants causing amino acid substitutions were found in 8 of the index cases with HCM. Five of them were identified as previously defined missense variants of Val698Ala, Arg719Trp, Met822Leu and Arg663Cys (in three cases) in the MYH7 gene, and Arg102Trp in the TNNT2 gene. For the first time in an HCM family with a history of late-onset SCD, Tyr525Asn and c.*27-21G> A variants in the MYBPC3 gene were identified as compound heterozygous. These variants were not present in control subjects (n=777) from the Turkish population. Conclusion: In this study, novel variants in the MYBPC3 gene were identified in an HCM family with SCD history. However, there was no clear association between pathogenic variants and the risk of SCD.