title: Identification of a genetic variant common to moyamoya disease and intracranial major artery stenosis/occlusion.
abstract: OBJECTIVE
  The c.14576G>A variant in ring finger protein 213 (RNF213) was recently identified as a susceptibility gene variant for moyamoya disease (MMD). The occurrence of c.14576G>A variant was evaluated in patients with intracranial major artery stenosis/occlusion (ICASO) without signs of MMD (non-MMD ICASO), as well as in patients with MMD and other cerebrovascular diseases as controls.
  
  
  METHODS
  This single-hospital-based case-control study was completed in 7 months (from October 2011-April 2012) at Department of Neurosurgery, The University of Tokyo Hospital. The occurrence of c.14576G>A variant was analyzed in 41 patients with non-MMD ICASO, in 48 with MMD, in 21 with cervical disease, in 61 with cerebral aneurysm, and in 25 normal subjects.
  
  
  RESULTS
  Nine of 41 patients (21.9%) with non-MMD ICASO and 41 of 48 (85.4%) with MMD had the c.14576G>A variant. One of 61 patients (1.6%) with cerebral aneurysm and no patients with cervical disease or normal subjects had the variant. Comparison of each phenotype group with the normal subjects showed that presence of c.14576G>A variant had significant associations with MMD (odds ratio [OR], 292.8; 95% confidence interval [CI], 15.4-5153.0; P<0.0001) and with non-MMD ICASO (OR, 14.9; 95% CI, 0.82-268.4; P=0.01), but no association with either cerebral aneurysm (OR, 1.2; 95% CI, 0.04-32.0; P=1.00) or cervical disease (OR, 1.1; 95% CI, 0.02-62.3; P=1.00).
  
  
  CONCLUSIONS
  The present study indicates that a particular subset of Japanese patients with non-MMD ICASO has a genetic variant associated with MMD. Therefore, we propose the existence of a new entity of ICASO caused by the c.14576G>A variant in RNF213.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Imai
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Takayanagi
authors.forename: Akitake
authors.initials: A
authors.lastname: Mukasa
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakatomi
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Saito
mesh_terms: D000251:Adenosine Triphosphatases; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D016022:Case-Control Studies; D002539:Cerebral Arterial Diseases / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009072:Moyamoya Disease / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases