title: Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population.
abstract: Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.
authors.affiliation: Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: S
authors.initials: S
authors.lastname: Tajima
authors.forename: M
authors.initials: M
authors.lastname: Harada-Shiba
authors.forename: T
authors.initials: T
authors.lastname: Yamamura
authors.forename: M
authors.initials: M
authors.lastname: Tsushima
authors.forename: B
authors.initials: B
authors.lastname: Kishino
authors.forename: Y
authors.initials: Y
authors.lastname: Horiguchi
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D005821:Genetic Techniques; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D011973:Receptors, LDL