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Strategy of ATP7B gene analysis for Japanese patients with Wilson disease, using ARMS method. ..................................

使用 ARMS 方法对日本威尔逊病患者进行 ATP7B 基因分析策略。

基本信息

批准号：
10670764
负责人：
SHIMIZU Norikazu
金额：
$ 2.11万
依托单位：
Toho Unversity School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

1. Molecular analysis for Wilson disease patients and Menkes disease patients in JapanWe analyzed ATP7B gene for 40 Japanese Wilson disease patients and ATP7A gene for 2 Japanese classical Menkes disease patients. R778L, A874V and 2871delC mutations were common mutations in Japanese Wilson disease patients.These 3 mutations could be found more than 50% of alleles. Also, we found novel mutation of Menkes disease patient, 2491insA. Mother of this patients had no mutation. Thus this mutation was de novo mutation.2. Genotype-phenotype correlation of Wilson diseaseAll of the patients who had R778L mutation homozygously were neurologic type of Wilson disease. Also all of patients who had 2871delC mutation homozygouly revealed severe liver dysfunction and/or progressive liver failure. We speculate that R778L mutation is specific for neurologic phenotype and 2871delC mutation causes svere hepatic damage.3. Copper specific P-type ATPase activityCopper-induced ATPase activities were measured relative to the lymphoblast cell lines derived from one case of classical Menkes disease patient and his mother, five Japanese patients with Wilson disease, and two normal subjects were investigated. Loss of copper-induced ATPase activities in lymphoblast were 29.1 ± 4.2% (Menkes disease patient), 48.2 ± 1.9% (his mother) and 42.7-60.8% (Wilson disease patients). In this study, copper-induced ATPase activities of Menkes disease patient, carrier of this disease and Wilson disease patients were definitely lower than that of normal subjects. This method will be useful as a functional analysis for copper metabolic disorders.

1.日本Wilson病和Menkes病患者的分子生物学分析我们对40例日本Wilson病患者的ATP 7 B基因和2例日本经典Menkes病患者的ATP 7A基因进行了分析。R778 L、A874 V和2871 delC突变是日本Wilson病患者常见的突变，这3种突变可在50%以上的等位基因中发现。此外，我们还发现了Menkes病患者的新突变，2491 insA。患者母亲无突变。因此，该突变为从头突变. Wilson病基因型与表型的相关性R778 L基因纯合突变的患者均为神经系统型Wilson病。所有2871 delC突变纯合的患者均显示严重肝功能障碍和/或进行性肝功能衰竭。我们推测R778 L突变是神经系统表型的特异性突变，2871 delC突变导致严重的肝损害.铜特异性P型ATP酶活性测定了1例典型Menkes病患者及其母亲、5例日本Wilson病患者和2例正常人的淋巴母细胞系铜诱导的ATP酶活性。铜诱导的淋巴母细胞ATP酶活性的丧失分别为29.1 ± 4.2%（Menkes病患者）、48.2 ± 1.9%（母亲）和42.7-60.8%（Wilson病患者）。门克斯病患者、携带者和Wilson病患者的铜诱导ATP酶活性均明显低于正常人。这种方法将是有用的功能分析铜代谢紊乱。