RNF213 as the major susceptibility gene for Chinese patients with moyamoya disease and its clinical relevance

Zhang, Qian; Liu, Yaping; Zhang, Dong; Wang, Rong; Zhang, Yan; Wang, Shuo; Yu, Lanbing; Lu, Chaoxia; Liu, Fang; Zhou, Jian; Zhang, Xue; Zhao, Jizong

doi:10.3171/2016.2.jns152173

Cited by 70 publications

(62 citation statements)

References 29 publications

(51 reference statements)

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“…Moreover, patients with a family history of MMD were more likely to carry the p.R4810K variant in the current study, and this result supported the results of some previous studies. 1,2,20 Interestingly, the ages of patients with family history were largely concentrated in the 5-9 age range, and these results coincided with that of Zhang et al, 21 who found that Chinese familial MMD can occur in patients and their third-degree relatives, of which firstdegree relatives are the most affected. Doctors should pay more attention to the family histories of patients with MMD during the process of diagnosis and expand the scope of screening in high-risk groups, especially younger patients.…”

Section: Discussionsupporting

confidence: 82%

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

et al. 2020

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ObjectivePrecise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease.MethodsA case–control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored.ResultsAn obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1–79.6; p = 1.6 × 10−141). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 × 10−7).ConclusionsStrong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

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Section: Discussionsupporting

confidence: 82%

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

et al. 2020

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“…The p.R4810K variant in RNF213 was identi ed as a founder variant with a strong susceptibility in MMD patients [15]. The p.R4810K mutation was found in 31.4% MMD patients in China [14], 75.8% MMD patients in Korea [16], and 95.1% MMD patients in Japan [10]. In present study, the incidence of p.R4810K variant in hemorrhagic MMD was 19.2%, which was much lower than the overall incidence.…”

Section: Discussioncontrasting

confidence: 46%

“…MMD was diagnosed according to the Japanese guidelines published in 2012 [13]. Patients who met the following criteria were included in this study: 1) p.R4810K variant was sequenced [14]. 2) Digital subtraction angiography (DSA) was received.…”

Section: Patients Datamentioning

confidence: 99%

Different Subtypes of Collateral Vessels in Hemorrhagic Moyamoya Disease with p.R4810K Variant

Zhang

et al. 2020

Preprint

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Background The aim of this study was to investigate the hemorrhgic sites and collateral vessels in hemorrhagic MMD with the p.R4810K variant.Methods Hemorrhage sites were classified as either anterior or posterior. Collateral vessels were classified into three subtypes according to origin: lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. Lenticulostriate anastomosis. Hemorrhage sites and collateral vessels were compared between patients with wild-type p.R4810K variant (GG) and patients with heterozygous p.R4810K variant (GA) after 1:1 propensity score matching.Results A total of 130 hemorrhagic MMD patients were included in present study, 21 pairs (42 hemorrhagic hemispheres) were obtained after 1:1 propensity score. In GA group, 16 hemispheres (76.2%) presented anterior hemorrhage, and 5 hemispheres (23.8%) presented with posterior hemorrhage. In GG group, 13 hemispheres (61.9%) presented anterior hemorrhage, and 8 hemispheres (38.1%) presented with posterior hemorrhage. No significant differences were found in hemorrhagic sites between two matched groups (P > 0.05). Of 21 hemispheres in GA group, 10 (47.6%) exhibited lenticulostriate anastomosis, 6 (28.6%) thalamic anastomosis, and 6 (28.6%) choroidal anastomosis. Of 21 hemispheres in GG group, 3 (14.3%) exhibited lenticulostriate anastomosis, 5 (23.8%) thalamic anastomosis, and 9 (42.9%) choroidal anastomosis. There was significant difference in lenticulostriate anastomosis between two matched groups (P = 0.045). After adjustment the age, sex, and PCA involvement, we found that lenticulostriate anastomosis was associated with p.R4810K variant (OR, 5.995; 95% CI, 1.296–27.737; P = 0.022).Conclusion Lenticulostriate anastomosis were associated with p.R4810K variant. Whereas hemorrhagic sites, thalamic anastomosis, and choroidal anastomosis were not correlated with p.R4810K variant.

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“…In our results, we found that RNF213 4810G > A (rs112735431) and 4950G > A (rs371441113) increased the likelihood of anterior ICASO. Both of these variants have been reported to be significantly associated with MMD in Korean and Chinese populations [18,21,40,41]. Similarly, there was a study of 221 Japanese patients, which found that RNF213 4810G > A was significantly associated with anterior ICASO but not posterior ICAS [42].…”

Section: Discussionmentioning

confidence: 86%

Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms

Kim

Park

Woo

et al. 2020

IJMS

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Intracranial major artery stenosis/occlusion (ICASO) is the major cause of ischemic stroke. Recent studies have suggested that variants of RNF213, a susceptibility gene for moyamoya disease (MMD), are also related to non-MMD ICASO. Regarding the predominant involvement of steno-occlusion on anterior circulation in MMD, we hypothesized that the ICASO distribution pattern (anterior/posterior) in non-MMD may differ according to RNF213 variants. This study analyzed 1024 consecutive Korean subjects without MMD who underwent computed tomography angiography (CTA) or magnetic resonance angiography (MRA). We evaluated four single nucleotide polymorphisms (SNPs) in the exon region of RNF213: 4448G > A (rs148731719), 4810G > A (rs112735431), 4863G > A (rs760732823), and 4950G > A (rs371441113). Associations between RNF213 variants and anterior/posterior ICASO were examined using multivariate logistic regression analysis. Anterior ICASO was present in 23.0% of study subjects, and posterior ICASO was present in 8.2%. The GA genotype of RNF213 4810G > A (adjusted odds ratio (AOR) [95% confidence interval (CI)], 2.39 [1.14–4.87] compared to GG; p = 0.018) and GA genotype of RNF213 4950G > A (AOR [95% CI], 1.71 [1.11–2.63] compared to GG; p = 0.015) were more frequent in subjects with anterior ICASO. The genotype frequency of RNF213 4863G > A differed significantly according to the presence of posterior ICASO. Further investigations of the functional and biological roles of RNF213 will improve our understanding of the pathomechanisms of ICASO and cerebrovascular disease.

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RNF213 as the major susceptibility gene for Chinese patients with moyamoya disease and its clinical relevance

Cited by 70 publications

References 29 publications

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease

Different Subtypes of Collateral Vessels in Hemorrhagic Moyamoya Disease with p.R4810K Variant

Distribution of Intracranial Major Artery Stenosis/Occlusion According to RNF213 Polymorphisms

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