Abstract:
The sudden death (SD) of a young and healthy individual can be traumatic. Approximately 85% of all SD cases are of cardiac origin, a condition known as sudden cardiac death (SCD). Familial dilated cardiomyopathy (FDCM) accounts for a major portion of SCD cases with the pathogenesis of FDCM being associated with changes in the main components of the nuclear lamina, within cardiac myocytes. These components - the lamins- are proteins encoded by the Lamin A/C (LMNA) gene. Causative variants of the LMNA gene are a major risk factor for SD and can be highly predictive for SCD. This study aimed to identify variations in the LMNA gene among SCD cases, within a cohort representative of the South African population. Two synonymous single nucleotide variants (SNVs) were identified in both case and control samples- SNV c.861T>C; p.Ala287 (rs535089) and SNV c.1338T>C; p.Asp446 (rs505058). Although previously classified as benign, these variants have been associated with dilated cardiomyopathy (DCM) and other laminopathy phenotypes. Due to their unique diagnostic value, inclusion of these variants in genetic screening panels can aid in confirming diagnosis of DCM and heart failure (HF), preventing SCD in young, otherwise healthy, individuals as well as aiding in further investigating other LMNA-associated diseases, which may arise as our population grows and diversifies.
