A de novo duplication in the low density lipoprotein receptor gene

Mutations in the low density lipoprotein receptor (LDLR) gene cause the autosomal dominant disease familial hypercholesterolemia (FH). The frequency of heterozygous FH, characterised by elevated cholesterol levels and an increased risk of coronary heart disease (CHD), is similar to 1/500 in most populations. South African Afrikaners have a particularly high frequency of FH (>1/100), due to three founder-related point mutations in the LDLR gene. During the course of screening hypercholesterolemics normal for these known mutations for defects in exon 4 of the LDLR gene, a de novo duplication of 18 base pairs was identified in one patient.