COMMON MUTATIONS IN THE LOW-DENSITY-LIPOPROTEIN-RECEPTOR GENE CAUSING FAMILIAL HYPERCHOLESTEROLEMIA IN THE JAPANESE POPULATION
COMMON MUTATIONS IN THE LOW-DENSITY-LIPOPROTEIN-RECEPTOR GENE CAUSING FAMILIAL HYPERCHOLESTEROLEMIA IN THE JAPANESE POPULATION
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DOI：
10.1161/01.atv.15.10.1713
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发表时间：
1995-10-01
影响因子：
8.7
通讯作者：
YAMAMOTO, A
中科院分区：
文献类型：
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作者：
MARUYAMA, T;MIYAKE, Y;YAMAMOTO, A
家族性高胆固醇血症（FH）是一种常见的遗传性疾病，由LDL受体基因突变引起。在本研究中，我们调查了四个日本FH纯合子，并确定了五个点突变：内含子12中的剪接位点突变（1845+2 T-->C突变），外显子7的错义突变（C317 S突变），外显子17的无义突变外显子14中的错义突变（P664 L突变）和外显子4中的错义突变（E119 K突变）。我们开发了检测这些突变的简单方法。我们在24例无血缘关系的FH纯合子中检测了这些突变的存在，其中7例发现1845+2 T-->C突变，另外4例突变在每个先证者中是独特的。我们还筛选了120例无关FH杂合子，发现1845+2 T-->C、C317 S、K790 X、P664 L和E119 K突变的频率分别为13.3%（16/120）、6.7%（8/120）、6.7%（8/120）、3.3%（4/120）和1.7%（2/120），分别这些突变在超过30%的无关日本FH患者中发现。通过使用本研究开发的检测方法，有望诊断出日本FH杂合子30%以上的遗传碱基。
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.