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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1713-1718.)
© 1995 American Heart Association, Inc.

Articles

Common Mutations in the Low-Density-Lipoprotein–Receptor Gene Causing Familial Hypercholesterolemia in the Japanese Population

Takao Maruyama; Yasuko Miyake; Shoji Tajima; Mariko Harada-Shiba; Taku Yamamura; Motoo Tsushima; Bun-ichiro Kishino; Yasunori Horiguchi; Tohru Funahashi; Yuji Matsuzawa; Akira Yamamoto

From the Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute (T.M., Y. Miyake, M.H.-S., T.Y., A.Y.); Institute for Protein Research, Osaka University (S.T.); Department of Internal Medicine, National Cardiovascular Center Hospital (M.T.); Department of Internal Medicine, Izumisano City Hospital (B-i.K.); Department of Pediatrics, Kitasato University Hospital (Y.H.); and Second Department of Internal Medicine, Osaka University Medical School (T.F., Y. Matsuzawa), Osaka, Japan.

Correspondence to Takao Maruyama, Department of Etiology and Pathophysiology, National Cardiovascular Center Research Institute, 5-7-1, Fujishiro-dai, Suita, Osaka 565, Japan.

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 TC 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 TC 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 TC, 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.

Key Words: LDL receptor • common mutation • Japanese • familial hypercholesterolemia

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