MUTATION ANALYSIS IN FAMILIAL HYPERCHOLESTEROLEMIA PATIENTS OF DIFFERENT ANCESTRIES - IDENTIFICATION OF 3 NOVEL LDLR GENE-MUTATIONS

Twelve familial hypercholesterolemia (FH) patients of different;ancest ries living in South Africa were subjected to mutation analysis of the low-density lipoprotein receptor (LDLR) gene. Nine different mutation s were identified in 10 patients. Six of these, including the founder- related mutation C660X identified in two Lebanese patients, have previ ously been described in other FH patients with compatible genetic back grounds, and/or in patients originating from countries where admixture is not uncommon. Characterization of an abnormal electrophoresis patt ern detected in exon 4 of the LDLR gene by heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, revealed a novel G dele tion at codon 185 (617delG) which resulted in a downstream stop codon. Two of the new mutations identified resulted in amino acid substituti ons and were designated R57C and Q357P. (C) 1998 Academic Press.