Wilson's disease
Wilson's disease
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DOI：
10.1016/s1542-3565(05)00484-2
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发表时间：
2005-08-01
影响因子：
12.6
通讯作者：
Ferenci, P
中科院分区：
文献类型：
--
作者：
Ferenci, P
威尔逊氏病（WD）是一种常染色体隐性遗传疾病，导致铜的肝内运输和胆汁排泄受损，导致铜在肝脏、角膜和脑等各器官积累。WD基因（OMIM 277900）编码铜转运p型atp酶（ATP7B）。虽然该基因的发现为了解WD的病理生理学带来了重大突破，但基因检测在WD患者临床管理中的作用尚未确立。诊断WD没有金标准。诊断需要临床和生化检查的结合。这些参数都不能单独诊断WD。为了便于诊断，2001年在德国莱比锡举行的第八届威尔逊病国际会议开发了一个评分系统。对于临床目的，突变分析的使用受到许多导致WD的突变（超过200个）的限制。与直接DNA测序相比，如果突变在人群中以合理的频率发生（例如，欧洲WD患者的H1069Q或远东WD患者的R778L），使用等位基因特异性探针进行直接突变检测是快速的，并且在临床上非常有用。迄今为止，突变分析是筛选具有已知致病突变的指示病例家族的唯一可靠工具。或者，单倍型分析可用于解决在区分杂合子基因携带者和受影响的无症状兄弟姐妹的诊断困境。
Wilson's disease (WD) is an autosomal recessive inherited disorder leading to impaired intrahepatic trafficking and biliary excretion of copper, resulting in the accumulation of copper in various organs including the liver, cornea, and brain. The WD gene (OMIM 277900) codes for a copper transporting P-type ATPase (ATP7B). Although the finding of the gene resulted in a major breakthrough for understanding the pathophysiology of WD, the role of genetic testing in the clinical management of WD patients is not yet established. There is no gold standard for diagnosis of WD. Diagnosis requires a combination of clinical and biochemical tests. None of these parameters alone allows a certain diagnosis of WD. To facilitate diagnosis, a scoring system was developed at the 8th International Meeting on Wilson Disease in Leipzig, Germany in 2001. For clinical purposes, the use of mutation analysis is limited by the occurrence of many mutations (more than 200) causing WD. In contrast to direct DNA sequencing, direct mutation detection by using allele-specific probes is rapid and clinically very helpful, if a mutation occurs with a reasonable frequency in the population (ie, H1069Q in European WD patients or R778L in WD patients from the Far East). To date, mutation analysis is the only reliable tool for screening the family of an index case with known causative mutation. Alternatively, haplotype analysis can be used to address diagnostic dilemmas in differentiating heterozygote gene carriers and affected asymptomatic siblings.