Positional cloning of the Warner's syndrome gene
Positional cloning of the Warner's syndrome gene
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DOI：
10.1126/science.272.5259.258
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发表时间：
1996-04-12
期刊：
影响因子：
56.9
通讯作者：
Schellenberg, GD
中科院分区：
文献类型：
--
作者：
Yu, CE;Oshima, J;Schellenberg, GD
沃纳综合征(WS)是一种遗传性疾病，临床症状类似于早衰。早期易患一些与年龄相关的重大疾病是这种疾病的一个主要特征。通过定位克隆鉴定了WS的致病基因(WRN)。预测的蛋白质全长1432个氨基酸，与DNA解旋酶有很大的相似性。在WS患者中发现了4个突变。其中两个突变是剪接连接突变，预测的结果是从最终的信使RNA中排除外显子。在接受检查的日本WS患者中，60%的患者发现其中一个突变，导致了移码和预测的蛋白质截断，处于纯合子状态。另外两个突变是无意义突变。一个突变的可能解旋酶是WS基因的基因产物，这表明DNA代谢缺陷参与了WS患者复杂的衰老过程。
Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.