WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.
WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.
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DOI：
10.1002/humu.23128
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发表时间：
2017-01
期刊：
影响因子：
3.9
通讯作者：
Oshima J
中科院分区：
文献类型：
--
作者：
Yokote K;Chanprasert S;Lee L;Eirich K;Takemoto M;Watanabe A;Koizumi N;Lessel D;Mori T;Hisama FM;Ladd PD;Angle B;Baris H;Cefle K;Palanduz S;Ozturk S;Chateau A;Deguchi K;Easwar TK;Federico A;Fox A;Grebe TA;Hay B;Nampoothiri S;Seiter K;Streeten E;Piña-Aguilar RE;Poke G;Poot M;Posmyk R;Martin GM;Kubisch C;Schindler D;Oshima J
沃纳综合征 (WS) 是一种罕见的常染色体隐性遗传疾病，其特征是一系列与内在生物衰老加速一致的成人发病表型。它是由 WRN 基因的致病性变异引起的，该基因编码具有核酸外切酶和解旋酶活性的多功能核蛋白。 WRN 蛋白被认为参与 DNA 代谢各个方面的优化，包括 DNA 修复、重组、复制和转录。在本次更新中，我们总结了总共 83 种不同的 WRN 突变，包括国际沃纳综合征登记处（华盛顿州西雅图）和日本沃纳联盟（日本千叶）鉴定的 8 种先前未发表的突变，以及文献中已报告的 75 种突变。西雅图国际登记处招募来自世界各地的患者来调查各种早衰综合症的遗传原因，以便为了解人类衰老的基本机制做出贡献。鉴于日本 WS 患者和杂合子携带者的患病率异常高，日本联盟的主要目标是开发有效的疗法并为日本和其他地方的 WS 患者制定管理指南。本综述还将讨论治疗这种疾病的潜在转化方法，包括目前正在研究的方法。
Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.