Familial hypercholesterolaemia caused by a non-sense mutation in codon 329 of the LDL receptor gene.

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