Moyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213.
RNF213 c.14576G>A variant was found in 1.8% (2/110) of the normal control group and had significant associations with definite MMD (P<0.0001; odds ratio, 144.0; 95% confidence interval, 26.7-775.9), unilateral MMD (P=0.0001; odds ratio, 54.0; 95% confidence interval, 7.5-386.8), and non-MMD ICASO (P<0.0001; odds ratio, 16.8; 95% confidence interval, 3.81-74.5).
Mysterin was originally isolated as a significant risk factor for the cryptogenic cerebrovascular disorder moyamoya disease, and was found to be involved in physiological angiogenesis in zebrafish.
RNF213 c.14576G>A was present in 10 of 43 patients in the anterior ICAS group and 4 of 5 patients in the MMD group, but was not present in the patients in the posterior ICAS and ECAS groups. c.14576G>A was found in 2 of 100 patients in the control group.
RNF213p.R4810K was identified as a susceptibility variant for moyamoya disease in Asia and non-moyamoya intracranial artery stenosis/occlusion disease in Japan and Korea recently.
A genetic analysis of RING-finger protein (RNF)-213, an MMD susceptibility gene, revealed that not only the patient, but also her sister, brother, and daughter had the heterozygous variant of the RNF-213 gene.
A significantly higher frequency of a heterozygous genotype was found in the TIMP2 promoter region at position -418 in FMMD; that is, the G/C heterozygous genotype at position -418 was observed in nine of 11 patients with FMMD, in 16 out of 50 nonfamilial MMD control participants, and in 14 out of 50 non-MMD control participants (FMMD versus nonfamilial MMD: odds ratio, 9.56; 95% confidence interval, 1.85-49.48; P = 0.005; and FMMD versus non-MMD: odds ratio, 10.50; 95% confidence interval, 2.02-54.55; P = 0.001).
A total of 69 RNF213 coding exons were directly sequenced in 18 probands and one relative who suffered from moyamoya disease in Slovakia and the Czech Republic.