Genetic Analysis of RNF213 c.14576G>A Variant in Nonatherosclerotic Quasi-Moyamoya Disease

Abstract

Background: Quasi-moyamoya disease (MMD) and MMD (definite MMD) have similar cerebral angiographic features, but whether these related diseases have similar etiology or genetic background remains unclear. Recently, we have reported that the recently identified MMD susceptibility gene variant RNF213 c.14576G>A (rs112735431) was associated with atherosclerotic intracranial major artery stenosis/occlusion. The present study investigated the occurrence of RNF213 c.14576G>A in patients with nonatherosclerotic quasi-MMD.

Methods: This study was a 2-hospital-based case-control study conducted at the Department of Neurosurgery, The University of Tokyo Hospital and Kanto Neurosurgical Hospital. A total of 87 Japanese patients who agreed to participate in this study were enrolled among both new and revisiting outpatients from October 2011 to December 2013 as follows: 78 patients with definite MMD and 9 patients with nonatherosclerotic quasi-MMD.

Results: The 9 patients with nonatherosclerotic quasi-MMD included 3 patients with previous irradiation, 2 with hyperthyroidism, 1 with Turner syndrome, 1 with meningitis, 1 with Behçet disease, and 1 with idiopathic pachymeningitis. The 78 patients with definite MMD included 66 patients (84.6%) with the c.14576G>A variant (64 heterozygotes and 2 homozygous). In contrast, no patients with nonatherosclerotic quasi-MMD had the variant.

Conclusions: Nonatherosclerotic quasi-MMD did not have RNF213 c.14576G>A variant. Moyamoya disease and related diseases might be classified by genetic analysis of the RNF213 c.14576G>A genotype. Further larger studies are required to confirm the present findings.

Keywords: Quasi-moyamoya disease; RNF213; genetics; moyamoya disease.