Abstract
Mutations in the LDL receptor (LDLR) cause familial hypercholesterolaemia (FH) in an autosomal dominant manner. The condition frequently progresses to coronary atherosclerosis. We describe a patient with FH, but without ischaemic heart disease, who had a novel frameshift mutation (327insC) in exon 4 of the LDLR gene. This mutation introduced a premature termination codon (TGA, codon 158). The patient was a 59-year-old man who had presented with hypercholesterolaemia and a plasma total cholesterol (TC) concentration of 12·2 mmol/L at age 44 years. The mutation 327insC in this patient was heterozygous and hypercholesterolaemia was common within his family. Despite taking lipid-lowering medications (probucol and pravastatin) for more than 20 years, his TC concentration hardly fell below 7·8 mmol/L. However, neither the patient nor anyone else in his family developed characteristic symptoms of ischaemic heart disease or xanthoma. This patient was discovered by an intensive mutation survey among 22 unrelated Japanese with FH mainly in the Kanto area of Japan, suggesting a low incidence of the mutation in the area.