A new horizon of moyamoya disease and associated health risks explored through RNF213.
A new horizon of moyamoya disease and associated health risks explored through RNF213.
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DOI：
10.1007/s12199-015-0498-7
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发表时间：
2016-03
影响因子：
4.7
通讯作者：
Youssefian S
中科院分区：
文献类型：
--
作者：
Koizumi A;Kobayashi H;Hitomi T;Harada KH;Habu T;Youssefian S
脑血管疾病烟雾病（MMD）于1957年首次在日本被描述，通常被认为是亚洲特有的疾病。然而，它是全球公认的儿童中风的主要原因之一。尽管已知几种单基因疾病与烟雾病血管病并发，但环指蛋白213基因（RNF 213）被鉴定为MMD的易感基因。RNF 213是不寻常的，因为（1）它诱导MMD而没有其他可识别的表型，（2）RNF 213 p.R4810K变体是日本人、韩国人和中国人常见的亚洲创始人突变，携带率为一般人群的0.5- 2%，但携带率低，（3）它编码具有双重AAA+ ATP酶和E3连接酶活性的相对最大的蛋白质。在这篇综述中，我们重点介绍了RNF 213的遗传学和遗传流行病学，RNF 213 R4810 K的病理学和RNF 213的分子功能，并讨论了公共卫生对目前尚未解决的MMD问题的贡献。我们还强调更新MMD定义的重要性，基于遗传流行病学的合格队列研究以及对与携带者基因检测相关的伦理问题的认识。本文的在线版本（doi：10.1007/s12199-015-0498-7）包含补充材料，可供授权用户使用。
The cerebrovascular disorder moyamoya disease (MMD) was first described in 1957 in Japan, and is typically considered to be an Asian-specific disease. However, it is globally recognized as one of the major causes of childhood stroke. Although several monogenic diseases are known to be complicated by Moyamoya angiopathy, the ring finger protein 213 gene (RNF213) was identified as a susceptibility gene for MMD. RNF213 is unusual, because (1) it induces MMD with no other recognizable phenotypes, (2) the RNF213 p.R4810K variant is an Asian founder mutation common to Japanese, Korean and Chinese with carrier rates of 0.5–2 % of the general population but a low penetrance, and (3) it encodes a relatively largest proteins with a dual AAA+ ATPase and E3 Ligase activities. In this review, we focus on the genetics and genetic epidemiology of RNF213, the pathology of RNF213 R4810K, and the molecular functions of RNF213, and also address the public health contributions to current unresolved issues of MMD. We also emphasize the importance of a more updated definition for MMD, of qualified cohort studies based on genetic epidemiology and an awareness of the ethical issues associated with genetic testing of carriers. The online version of this article (doi:10.1007/s12199-015-0498-7) contains supplementary material, which is available to authorized users.