Monogenic primary hypercholesterolaemia in South Africa.

Familial hypercholesterolaemia (FH) and familial defective apolipoprotein B-100 (FDB) are the two major causes of monogenic primary hypercholesterolaemia. In this review, FH and FDB are defined in relation to normal lipoprotein metabolism. In South Africa FH affects about 1% of Afrikaners, Jews and Indians, while FDB is probably a much rarer disorder. In Afrikaners, three 'founder' mutations are responsible for more than 80% of FH. The population genetics that created the exceptionally high frequency of FH and comparatively low frequency of FDB in various South African populations are described. The genetic organisation and itinerary of the normal low-density lipoprotein (LDL) receptor are reviewed, with particular emphasis on the structure-function relationships in the LDL receptor that have been clarified by the mutations found in South Africa. Finally, the clinical relevance of research into FH in South Africa is discussed.