DNA screening of hyperlipidemic Afrikaners for familial hypercholesterolemia.

Three different point mutations of the low-density lipoprotein receptor (LDLR) gene are responsible for familial hypercholesterolemia (FH) in about 90% of Afrikaner patients. Screening of hyperlipidemic Afrikaner individuals for these founder-related mutations was performed to determine the distribution of the mutations in individuals with different lipid profiles, and to provide guidelines for screening of the mutations in hyperlipidemics. Rapid DNA methods, based on restriction enzyme analysis or allele-specific hybridisation of enzymatically-amplified genomic DNA, have been used to analyse the LDLR gene mutations in four groups of Afrikaner individuals. Group 1 included 84 individuals in whom FH was diagnosed on clinical data. Groups 2-4 included 89 hyperlipidemic individuals who did not fulfil the criteria for inclusion in the FH study group. The founder-related LDLR gene mutations were present in 36% of the hyperlipidemics whose clinical diagnosis excluded them from the FH study group. This indicates that conventional methods for the diagnosis of FH, based mainly on lipid determinations and a family history of coronary heart disease, do not always allow an accurate diagnosis of the disease. Screening of hyperlipidemic Afrikaner individuals for specific founder-related LDLR gene mutations can provide a definite diagnosis of FH, which may lead to better counselling and optimal treatment.