Familial hypercholesterolemia: potential diagnostic value of mutation screening in a pediatric population of South Africa.

Three founder-related low-density lipoprotein receptor (LDLR) gene mutations, D154N, D206E and V408M, cause familial hypercholesterolemia (FH) in approximately 90% of South African Afrikaners. Two hundred and twenty-one South African children, from 85 affected families, were screened 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 were similar among the children heterozygous for the three founder mutations, and mean values were significantly higher compared to those without a known mutation (p < 0.0001). Plasma cholesterol levels overlapped considerably between the different groups, suggesting that modifiable lifestyle factors remain important in children with FH. This study demonstrates the potential diagnostic value of mutation screening in a pediatric population with an enrichment of particular gene mutations.