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.日本威尔逊病和门克斯病患者的分子分析我们分析了40名日本威尔逊病患者的ATP7B基因和2名日本经典门克斯病患者的ATP7A基因R778L、A874V和2871delC突变是日本威尔逊病患者的常见突变。超过50%的等位基因有3个突变，我们还发现了门克斯病患者母亲的新突变，2491insA。 2．R778L纯合突变患者均为神经型Wilson病，2871delC纯合突变患者均为神经型。肝功能障碍和/或进行性肝功能衰竭我们推测R778L突变是神经表型特有的，而2871delC突变会导致严重的肝损伤。3．铜特异性 P 型 ATP 酶活性铜诱导的 ATP 酶活性是相对于来自一名经典门克斯病患者及其母亲、五名日本威尔逊病患者以及两名正常受试者的淋巴母细胞系进行测量的。淋巴母细胞中诱导的 ATP 酶活性分别为 29.1 ± 4.2%（门克斯病患者）、48.2 ± 1.9%（他的母亲）和 42.7-60.8% （威尔逊病患者）在本研究中，门克斯病患者、该病携带者和威尔逊病患者的铜诱导的 ATP 酶活性明显低于正常受试者，该方法可用于铜代谢紊乱的功能分析。。