Xue Yimeng, Zeng Chaofan, Ge Peicong, Liu Chenglong, Li Junsheng, Zhang Yan, Zhang Dong, Zhang Qian, Zhao Jizong
Savaid Medical School, University of Chinese Academy of Sciences, Beijing (Y.X., J.Z.).
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China (Y.X., C.Z., P.G., C.L., J.L., Y.Z., D.Z., Q.Z., J.Z.).
Stroke. 2022 Sep;53(9):2906-2916. doi: 10.1161/STROKEAHA.121.038066. Epub 2022 May 11.
The pathogenic mechanisms of periventricular anastomosis (PA) in moyamoya disease remain unknown. Here, we aimed to describe the angiographic profiles of PA and their relationships with really interesting new gene (RING) finger protein 213 (RNF213) genotypes.
We conducted a retrospective cohort study of moyamoya disease patients consecutively recruited between June 2019 and January 2021 in Beijing Tiantan Hospital, Capital Medical University, China. C-terminal region of RNF213 was sequenced. Angiographic characteristics of PA vessels (lenticulostriate artery, thalamotuberal artery, thalamoperforating artery, anterior choroidal artery, and posterior choroidal artery) were compared between different groups of genotypes. The dilatation and extension of PA vessels were measured by using PA score (positive, score 1-5; negative, score 0). Multivariate regression analysis was conducted to assess variables associated with PA score. In addition, gene expression of RNF213 in human brain regions was evaluated from the Allen Human Brain Atlas.
Among 260 patients (484 hemispheres), 71.2% carried no rare and novel variants, 20.0% carried p.R4810K heterozygotes, and 8.8% carried other rare and novel variants. PA scores in patients with p.R4810K and other rare and novel variants were significantly higher than in wild-type patients (<0.001). Age (odds ratio [OR], 0.958 [95% CI, 0.942-0.974]; <0.001), platelet count (OR, 0.996 [95% CI, 0.992-0.999]; =0.027), p.R4810K variant (OR, 2.653 [95% CI, 1.514-4.649]; =0.001), other rare and novel variants (OR, 3.197 [95% CI, 1.012-10.094]; =0.048), Suzuki stage ≥4 (OR, 1.941 [95% CI, 1.138-3.309]; =0.015), and posterior cerebral artery involvement (OR, 1.827 [95% CI, 1.020-3.271]; =0.043) were significantly correlated with PA score. High expression of RNF213 was detected in the periventricular area.
variants were confirmed to be associated with PA in moyamoya disease. Individuals with p.R4810K heterozygotes and other C-terminal region rare variants exhibited different angiographic phenotypes, compared with wild-type patients.
烟雾病中脑室周围吻合（PA）的致病机制尚不清楚。在此，我们旨在描述PA的血管造影特征及其与真有趣新基因（RING）指蛋白213（RNF213）基因型的关系。
我们对2019年6月至2021年1月在中国首都医科大学附属北京天坛医院连续招募的烟雾病患者进行了一项回顾性队列研究。对RNF213的C末端区域进行测序。比较不同基因型组之间PA血管（豆纹动脉、丘脑结节动脉、丘脑穿通动脉、脉络膜前动脉和脉络膜后动脉）的血管造影特征。使用PA评分（阳性，评分1 - 5；阴性，评分0）测量PA血管的扩张和延伸。进行多变量回归分析以评估与PA评分相关的变量。此外，从艾伦人类脑图谱评估RNF213在人脑区域的基因表达。
在260名患者（484个半球）中，71.2%未携带罕见和新变异，20.0%携带p.R4810K杂合子，8.8%携带其他罕见和新变异。携带p.R4810K和其他罕见及新变异的患者的PA评分显著高于野生型患者（<0.001）。年龄（比值比[OR]，0.958[95%置信区间，0.942 - 0.974]；<0.001）、血小板计数（OR，0.996[95%置信区间，0.992 - 0.999]；=0.027）、p.R4810K变异（OR，2.653[95%置信区间，1.514 - 4.649]；=0.001）、其他罕见和新变异（OR，3.197[95%置信区间，1.012 - 10.094]；=0.048）、铃木分期≥4（OR，1.941[95%置信区间，1.138 - 3.309]；=0.015）和大脑后动脉受累（OR，1.827[95%置信区间，1.020 - 3.271]；=0.043）与PA评分显著相关。在脑室周围区域检测到RNF213的高表达。
已证实变异与烟雾病中的PA相关。与野生型患者相比，携带p.R4810K杂合子和其他C末端区域罕见变异的个体表现出不同的血管造影表型。
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