Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene.
Genetics and Biomarkers of Moyamoya Disease: Significance of RNF213 as a Susceptibility Gene.
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DOI：
10.5853/jos.2014.16.2.65
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发表时间：
2014-05
影响因子：
8.2
通讯作者：
Tominaga T
中科院分区：
文献类型：
--
作者：
Fujimura M;Sonobe S;Nishijima Y;Niizuma K;Sakata H;Kure S;Tominaga T
Moyamoya病的特征是在颈内动脉末端部分的进行性狭窄和在大脑底部的异常血管网络。虽然其病因尚不清楚，但最近的全基因组和位点特异性关联研究确定RNF 213是东亚人群烟雾病的重要易感基因。RNF 213中c.14576G>A的多态性在95%的烟雾病家族性患者和79%的散发病例中被鉴定，并且发现具有该多态性的患者具有显著更早的疾病发作和更严重的烟雾病形式，如脑梗死和大脑后动脉狭窄的表现。RNF 213异常与烟雾病相关的确切机制仍然未知，而最近的报告使用通过同源重组缺乏RNF 213的基因工程小鼠为这种罕见实体的发病机制提供了新的见解。在烟雾病的生物标志物方面，烟雾病的特征是血管生成因子和促炎分子如血管内皮生长因子和基质金属蛋白酶-9的表达增加，这可能部分解释了其病理性血管生成、自发性出血和血运重建手术后脑过度灌注发生率较高的临床表现。最近，在围手术期阻断这些促炎分子试图降低手术并发症（包括脑过度灌注综合征）的潜在风险。本文就烟雾病的遗传学和生物标志物及其临床意义作一综述。
Moyamoya disease is characterized by a progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology is still unknown, recent genome-wide and locus-specific association studies identified RNF213 as an important susceptibility gene of moyamoya disease among East Asian population. A polymorphism in c.14576G>A in RNF213 was identified in 95% of familial patients with moyamoya disease and 79% of sporadic cases, and patients having this polymorphism were found to have significantly earlier disease onset and a more severe form of moyamoya disease, such as the presentation of cerebral infarction and posterior cerebral artery stenosis. The exact mechanism by which the RNF213 abnormality relates to moyamoya disease remains unknown, while recent reports using genetically engineered mice lacking RNF213 by homologous recombination provide new insight for the pathogenesis of this rare entity. Regarding biomarkers of moyamoya disease, moyamoya disease is characterized by an increased expression of angiogenic factors and pro-inflammatory molecules such as vascular endothelial growth factors and matrix metalloproteinase-9, which may partly explain its clinical manifestations of the pathologic angiogenesis, spontaneous hemorrhage, and higher incidence of cerebral hyperperfusion after revascularization surgery. More recently, blockade of these pro-inflammatory molecules during perioperative period is attempted to reduce the potential risk of surgical complication including cerebral hyperperfusion syndrome. In this review article, we focus on the genetics and biomarkers of moyamoya disease, and sought to discuss their clinical implication.
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DOI：
10.1161/01.atv.17.10.2238
发表时间：
1997-10-01
影响因子：
8.7
作者：
Kumar, A;Lindner, V
通讯作者：
Lindner, V
影响因子：
2.3
作者：
Fukui, M;Kono, S;Ikezaki, K
通讯作者：
Ikezaki, K
影响因子：
--
作者：
Fujimura, Miki;Mugikura, Shun;Tominaga, Teiji
通讯作者：
Tominaga, Teiji
影响因子：
3.7
作者：
Liu W;Morito D;Takashima S;Mineharu Y;Kobayashi H;Hitomi T;Hashikata H;Matsuura N;Yamazaki S;Toyoda A;Kikuta K;Takagi Y;Harada KH;Fujiyama A;Herzig R;Krischek B;Zou L;Kim JE;Kitakaze M;Miyamoto S;Nagata K;Hashimoto N;Koizumi A
通讯作者：
Koizumi A
影响因子：
3.7
作者：
Park YS;Jeon YJ;Kim HS;Chae KY;Oh SH;Han IB;Kim HS;Kim WC;Kim OJ;Kim TG;Choi JU;Kim DS;Kim NK
通讯作者：
Kim NK