MOLECULAR DISSECTION OF CARDIOMYOPATHY

Abstract

Hypertrophic (HCM) and dilated cardiomyopathy (DCM) are inherited cardiac conditions with marked genetic heterogeneity. The genetic aetiology of HCM and DCM in Singapore and European was broadly similar but Singapore Chinese HCM patients frequently have fewer clinically actionable disease variants, overall. Two common lowly penetrant risk alleles (TNNT2:p.Arg286His and TNNI3:p.Arg79Cys) were enriched in Singapore HCM and reclassified based on new functional and populational evidences. It is expected to change the clinical management of a theoretical 400 and 200,000 cases of HCM in Singapore and China respectively. In cardiac MRI study, genotype-positive HCM patients had more fibrosis but smaller indexed left ventricular mass. While in DCM, 10.7% Singapore cases carried TTN truncating variants and another 10% carried pathogenic HCM variants suggesting burnt-out HCM. Non-truncating TTN variants along TTN Z-disk were enriched in Singapore DCM cases. These data highlight the need for greater study of HCM and DCM genetics in non-European populations.