FAMILIAL HYPERCHOLESTEROLEMIA - POTENTIAL DIAGNOSTIC-VALUE OF MUTATION SCREENING IN A PEDIATRIC POPULATION OF SOUTH-AFRICA

Three founder-related low-density lipoprotein receptor (LDLR) gene mut ations, D154N, D206E and V408M, cause familial hypercholesterolemia (F H) in approximately 90% of South African Afrikaners. Two hundred and t wenty-one South African children, from 85 affected families, were scre ened for the specific mutation identified previously in the index case . Sixty boys and 56 girls were heterozygous for mutation D154N (FH3), D206E (FH1) or V408M (FH2). Total and LDL cholesterol (LDLC) levels we re similar among the children heterozygous for the three founder mutat ions, and mean values were significantly higher compared to those with out a known mutation (p < 0.0001). Plasma cholesterol levels overlappe d considerably between the different groups, suggesting that modifiabl e lifestyle factors remain important in children with FH. This study d emonstrates the potential diagnostic value of mutation screening in a pediatric population with an enrichment of particular gene mutations. (C) Munksgaard, 1998.