Prenatal diagnosis of familial hypercholesterolemia: Importance of DNA analysis in the high-risk South African population

In this report on the outcome of the first prenatal diagnosis performed for familial hypercholesterolemia (FH) in a South African family, we aim to de monstrate the value of a population-directed screening strategy to identify FH patients in populations with an enrichment for certain low-density lipo protein receptor (LDLR) gene mutations. Prenatal diagnosis was offered to a n Afrikaner couple, both partners heterozygous for the PH mutation D206E, w hose first child was diagnosed with heterozygous FH and the second with hom ozygous FH. Genomic DNA isolated from parental peripheral blood and subsequ ently amniotic fluid was amplified by the polymerase chain reaction (PCR) a nd subjected to mutation analysis. Heterozygosity for mutation D206E was co nfirmed in both parents, whilst this mutation was not detected in DNA direc tly amplified from amniotic fluid. To exclude the possibility of a false-ne gative result due to the limited number of cells in the uncultured amniotic fluid sample, cells were also cultured in vitro, and the DNA extracted and subjected to a second round of analysis, This confirmed the absence of mut ation D206E in the fetus. This case illustrates the application of a DNA-ba sed mutation detection technique as a simple and rapid diagnostic aid that can be carried out at a relatively early gestational stage. Prenatal diagno sis of FH, aimed at the detection of homozygous cases, is particularly feas ible in populations and families with molecularly defined LDLR gene mutatio ns.