title: Hypertrophic cardiomyopathy repealing tenets in South Africa.
abstract: Hypertrophic cardiomyopathy (HCM), a common primary cardiac disorder with an increased risk of sudden death, affects all population groups in South Africa. Distinct causal mutations in multiple sarcomeric protein-encoding genes correlate with the risk of sudden death. Such genotype/phenotype correlations cannot be extrapolated geographically or ethnically, necessitating the generation of South African-specific data. We used DNA-based techniques to search for the causal mutations in a panel of South African HCM-affected subjects (37 with unequivocal HCM, 47 with HCM-like disease). Mutations detected were traced in family members and carriers assessed by echocardiography and electrocardiography. Nine different HCM-causing mutations (5 unique to South Africa, 3 showing a founder effect) were identified in 3 genes in 24 index cases (57% HCM group, 6% HCM-like group). The different mutations were associated with variable hypertrophy, independent of the risk of sudden death. The disease was generally familial and many at-risk mutation carriers did not meet clinical diagnostic criteria for HCM. Rigorous diagnosis of index cases facilitates detection of causal mutations, which allows for unequivocal DNA-based diagnosis of at-risk family members, regardless of age or clinical status. This permits focused patient management, informed prognostication and realistic counselling for this insidious disease, as well as time and cost savings.
authors.forename: J. C.
authors.initials: JC
authors.lastname: Moolman-Smook
authors.initials: J
authors.lastname: De Lange
authors.initials: A
authors.lastname: Brink
authors.initials: A
authors.lastname: Corfield