title: Japanese familial hypercholesterolaemia with a 327insC mutation in the LDL receptor gene.
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.
authors.affiliation: Department of Clinical Pathology, Omiya Medical Center, Jichi Medical School, Saitama Prefecture 330-8503, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hirota
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kubo
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hikiji
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakajima
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Hata
authors.forename: Ikunosuke
authors.initials: I
authors.lastname: Sakurabayashi
mesh_terms: D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005091:Exons; D016368:Frameshift Mutation / Q000235:genetics*; D020180:Heteroduplex Analysis / Q000379:methods; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics*; D007564:Japan; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*; D013997:Time Factors
chemical_list: D008055:Lipids; D011973:Receptors, LDL