Report on a molecular diagnostic service for familial hypercholesterolemia in Afrikaners.

The development of DNA-based methods for the direct detection of specific low density lipoprotein receptor (LDLR) gene mutations enabled us to establish a molecular diagnostic service for familial hypercholesterolemia (FH). This specialised service is of particular relevance and can be applied in the Afrikaner population of South Africa, where a founder gene effect increased the prevalence of FH to about 5-10 times greater than that found in most other population groups. Three point mutations in the LDLR gene were shown to account for approximately 90% of all Afrikaner FH cases. We report on the results obtained in 354 Afrikaner hyperlipidemics, from 274 unrelated families, referred for mutation screening-during the four-year period following the elucidation of the molecular basis of FH in this South African population group. By screening for the three founder-related LDLR gene mutations, approximately 50% of referrals were diagnosed as having FH. Presymptomatic diagnosis of FH by DNA analysis overcame the difficulties involved in the clinical diagnosis of some heterozygous cases. We could offer appropriate genetic counselling to FH patients, in addition to optimal clinical management by clinicians who referred the patients. Genetic testing has made early diagnosis of FH, including prenatal diagnosis, a reality.