FAMILIAL HYPERCHOLESTEROLEMIA CAUSED BY A NONSENSE MUTATION IN CODON-329 OF THE LDL RECEPTOR GENE

Analysis of single-strand conformation polymorphisms (SSCP) was employ ed to screen familial hypercholesterolaemia (FH) subjects for point mu tations in exon 7 of the low density lipoprotein receptor (LDLR) gene. An abnormal band pattern was found in one out of 100 unrelated FH sub jects. The underlying mutation was found by DNA sequencing to be due t o heterozygosity (C/T) at nucleotide 1048. Nucleotide 1048 is the firs t nucleotide of codon 329, and is located within the domain that has a high degree of homology with the precursor for epidermal growth facto r. The C --> T transition, referred to as FH-Fossum, changes codon 329 from CGA(Arg) to TGA(Stop). The mutation is expected to cause a class 1 receptor defect.