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。日本威尔逊病患者和Menkes病患者的分子分析分析了40名日本威尔逊病患者的ATP7B基因和2名日本古典Menkes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。这三个突变可以发现超过50％的等位基因。另外，我们发现了Menkes病患者的新型突变，2491INSA。该患者的母亲没有突变。该突变是从头突变。2。威尔逊疾病的基因型 - 表型相关性所有患有R778L突变的患者是纯合的Wilson病的神经系统类型。同样，所有患有2871DELC突变纯合性的患者均显示出严重的肝功能障碍和/或进行性肝衰竭。我们推测R778L突变是神经系统型的特异性，而2871DELC突变会造成肝损伤。3。相对于从一例古典Menkes疾病患者及其母亲，五名日本威尔逊病患者的淋巴细胞细胞系，对铜特异性P型ATPase ATPase Attpase诱导的ATPase活性进行了测量，并研究了两个正常受试者。铜细胞中铜诱导的ATPase活性的损失为29.1±4.2％（Menkes病患者），48.2±1.9％（他的母亲）和42.7-60.8％（威尔逊病患者）。在这项研究中，铜诱导的Menkes疾病患者的ATPase活性，该疾病的携带者和Wilson病患者的患者绝对低于正常受试者。该方法可作为铜代谢性疾病的功能分析。