Novel mutations of the ATP7B gene in Japanese patients with Wilson disease
Novel mutations of the ATP7B gene in Japanese patients with Wilson disease
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DOI：
10.1007/s100380050017
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发表时间：
2000-01-01
影响因子：
3.5
通讯作者：
Sakata, T
中科院分区：
文献类型：
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作者：
Kusuda, Y;Hamaguchi, K;Sakata, T
威尔逊病（WD）是一种常染色体隐性遗传病，其特征是铜在肝脏、大脑、肾脏和角膜中积累，并最终导致这些器官中的铜中毒。在这项研究中，我们分析了4名日本WD患者中负责基因ATP7B的突变。通过直接测序，我们鉴定出5个突变，其中2个是新的；16个多态性，其中6个是新的。突变2871delC和2513de1A使阅读框移位，因此预期出现截断的异常蛋白。与早发肝型患者的突变相反，突变A874V、R778L和3892delGTC为错义突变或框内1氨基酸缺失，发生在晚发肝神经型患者中。2871delC和R778L突变先前在相对大量的日本患者中有报道。特别是，R778L在亚洲国家比在世界其他国家更为普遍。我们的数据与突变倾向于以特定人群的方式发生的假设是一致的。因此，积累日本WD患者的突变类型，有助于对日本WD患者进行快速有效的基因诊断。
Wilson disease (WD) is an autosomal recessive disorder characterized by copper accumulation in the liver, brain, kidneys, and corneas, and culminating in copper toxication in these organs. In this study, we analyzed mutations of the responsible gene, ATP7B, in four Japanese patients with WD. By direct sequencing, we identified five mutations, of which two were novel, and 16 polymorphisms, of which 6 were novel. The mutations 2871delC and 2513de1A shift the reading frame so that truncated abnormal protein is expected. In contrast to these mutations found in patients with hepatic-type of early onset, the mutations A874V, R778L, and 3892delGTC were either missense mutations or inframe 1-amino acid deletion, and occurred in the patients with hepato-neurologic type of late onset. The mutations 2871delC and R778L have been previously reported in a relatively large number of Japanese patients. In particular, R778L is known to be more prevalent in Asian countries than in other countries of the world. Our data are compatible with the hypothesis that the mutations tend to occur in a population-specific manner. Therefore, the accumulation of the types of mutations in Japanese patients with WD will facilitate the fast and effective genetic diagnosis of WD in Japanese patients.