Fujimura Miki
Department of Neurosurgery, Hokkaido University Graduate School of Medicine.
No Shinkei Geka. 2022 Jan;50(1):216-221. doi: 10.11477/mf.1436204546.
Moyamoya disease(MMD)is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis at the internal carotid artery terminus and abnormal vascular network formation at the base of the brain. Although its etiology is still unknown, recent genetic analysis identified as an important susceptibility gene for MMD. A single nucleotide polymorphism in c.14576G>A(p.R4810K)in was identified in 80% of patients with MMD in Japan, and RNF213 mutation was found to be significantly associated with earlier disease onset and more severe disease. More recent studies identified a significant correlation between RNF213 mutation and the intrinsic cerebral hemodynamics, such as local cerebral hyperperfusion after direct revascularization surgery for patients with MMD. These results indicate that RNF213 could be a useful biomarker for the prediction of the clinical course of MMD and/or the outcomes of revascularization surgery. Further investigation is warranted to clarify the exact mechanism by which RNF213 mutation leads to the steno-occlusive changes at the internal carotid artery terminus, development of abnormal vascular networks at the base of the brain, and ultimate cerebrovascular events in patients with MMD. This information could also be helpful in the implementation of precision medicine by providing critical information regarding the molecular target candidates in the management of MMD.
烟雾病（MMD）是一种慢性闭塞性脑血管疾病，其特征是颈内动脉末端进行性狭窄以及脑底部异常血管网形成。尽管其病因仍不明确，但最近的基因分析确定 为烟雾病的一个重要易感基因。在日本，80%的烟雾病患者中发现了 基因c.14576G>A（p.R4810K）处的单核苷酸多态性，并且发现RNF213突变与疾病更早发作和更严重病情显著相关。最近的研究还发现RNF213突变与内在脑血流动力学之间存在显著相关性，例如烟雾病患者直接血运重建手术后的局部脑血流过度灌注。这些结果表明，RNF213可能是预测烟雾病临床病程和/或血运重建手术结果的有用生物标志物。有必要进一步研究以阐明RNF213突变导致烟雾病患者颈内动脉末端狭窄闭塞性改变、脑底部异常血管网形成以及最终脑血管事件的确切机制。这些信息通过提供有关烟雾病管理中分子靶点候选物的关键信息，也可能有助于精准医学的实施。
