The molecular basis and diagnosis of familial hypercholesterolaemia in South African Afrikaners.

Three different point mutations were recently identified in South African familial hypercholesterolaemics. These mutations result in the modification of recognition sites of specific restriction endonucleases. This study describes rapid methods for presymptomatic detection of these defects based on restriction enzyme analysis or allele-specific hybridization of enzymatically amplified genomic DNA. These methods were used to determine the frequencies of the three known low-density lipoprotein (LDL) receptor gene mutations in 138 chromosomes of Afrikaner FH patients. It has been shown that a common mutation at the 3' end of exon 4 (base 681) of the LDL receptor gene is present in about 70% of alleles, while the mutations in exons 9 (base 1285) and 4 (base 523) of the gene are present in about 20 and 10% respectively of the genes studied. These mutations were found in approximately 95% of Afrikaner familial hypercholesterolaemic patients studied, indicating at least three founder members for the disease in this population of South Africa.