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Background and Purpose. Recently, several studies indicated the c.14576G>A variant on the ring finger protein 213 (RNF213), a founder variant of moyamoya diseases (MMD), was associated with non-MMD intracranial major artery stenosis/occlusion (non-MMD ICASO). We proposed that RNF213 variant-related ICASO including MMD might be a special entity with its own characteristics based on a genetic background. The aim of the study was to learn the clinical and vascular features of RNF213 variant-related ICASO. Moreover, we tried to explore the clinical significance of a testing variant in ICASO patients in China. Methods. Clinical material and routine image data were collected in 160 Chinese patients with ICASO, including 41 verified MMD and 119 non-MMD. DNA samples were extracted, and the c.14576G>A variant on RNF213 was genotyped. Then, the clinical and vascular features were compared between the patients with and without a relevant variant. Furthermore, the patients with RNF213 mutation were performed with high resolution magnetic resonance imaging (HR-MRI) examination to conclude features of the artery wall. Results. There were 16 (10%) patients (including 9 MMD and 7 non-MMD ICASO) presenting a heterozygous c.14576G>A variant while none of homozygote was found. Compared to the patients without the c.14576G>A variant, the variant group had more female, less symptomatic patients, and more possibility of having collateral vessels in vascular imaging. In the symptomatic subgroup, there is no significant difference in clinical presentation (p>0.05) between two groups. However, RNF213 variant-related ICASO had lower scores in NIHSS (1.0±3.0 vs. 3.9±5.0, p<0.05) but not in mRS. In the symptomatic subgroup, in addition, most of the HR-MRI images of variant ICASO (77.8%, 7 of 9) were characterized by a shrunken outer diameter, concentric thickening vessel wall, and collateral vessel structures on the stenotic portion, which was prone to be diagnosed as HR-MMD (a MMD diagnosis diagnosed by HR-MRI). The rest of the two variants showed a relatively eccentric luminal narrow, normal outer diameter without collateral vessel findings, identified as HR-ICAD (intracranial atherosclerotic disease diagnosed by HR-MRI). Conclusions. Our study demonstrated that the c.14576G>A variant on RNF213 may be a biomarker to good outcome of ICASO in Chinese. The variant-related ICASO was characterized by both features of MMD and ICAD diagnosed by HR-MRI. [ABSTRACT FROM AUTHOR]

Background and Purpose: The ring finger protein 213 (RNF213) gene R4810K variant, a susceptibility locus for moyamoya disease (MMD), has recently been identified to be associated with intracranial major artery stenosis/occlusion (ICASO) without satisfying the diagnostic criteria of MMD in the Japanese population. However, further studies are needed to determine whether this variant is associated with ICASO in other populations and whether R4810K variant-related ICASO could be categorized as MMD. The aim of this study is to elucidate whether the R4810K variant was associated with ICASO among the Han Chinese population and potential histopathology of R4810K variant-related ICASO., Materials and Methods: We conducted a case-control study to evaluate association and performed high-resolution (HR) magnetic resonance imaging (MRI) to investigate arterial wall feature of ICASO. The R4810K variant was genotyped in 114 ICASO patients and 268 controls. Then, patients with R4810K variant-related ICASO were subjected to HR MRI examination and presumptively diagnosed based on the characteristics thus observed., Statistical Analysis: The relationship between R4810K variant and ICASO was evaluated by Fisher's exact test with odds ratios (OR) and 95% confidence interval (CI)., Results: The R4810K variant was associated with ICASO and increased the risk for ICASO ( P < 0.01; OR: 20.2; 95% CI: 2.5-163.11). Presumptive MMD was diagnosed in all female patients with R4810K variant. However, presumptive intracranial atherosclerotic stenosis was diagnosed in one of three males harboring this variant., Conclusions: The R4810K variant is a genetic risk factor for ICASO among the Han Chinese population and that R4810K variant-related ICASO should be identified as MMD in female but not uncertain in male patients., Competing Interests: There are no conflicts of interest.