title: Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1.
abstract: OBJECTIVE In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not. METHODS The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing. RESULTS In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57-1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement. CONCLUSIONS The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1-moyamoya connection.
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Ji Hoon
authors: JH
authors: Phi
authors: Department of Neurosurgery, Samsung Medical Center;
authors: Jung Won
authors: JW
authors: Choi
authors: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine;
authors: Moon-Woo
authors: MW
authors: Seong
authors: Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, Gyeonggi-do; and.
authors: Tackeun
authors: T
authors: Kim
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Youn Joo
authors: YJ
authors: Moon
authors: Medical Research Collaborating Center, Seoul National University Hospital;
authors: Joongyub
authors: J
authors: Lee
authors: Department of Neurosurgery, Dongguk University Ilsan Hospital, Goyang, Gyeonggi-do, Republic of Korea.
authors: Eun Jung
authors: EJ
authors: Koh
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Seul Ki
authors: SK
authors: Ryu
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Tae Hee
authors: TH
authors: Kang
authors: Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, Gyeonggi-do; and.
authors: Jae Seung
authors: JS
authors: Bang
authors: Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Sungnam, Gyeonggi-do; and.
authors: Chang Wan
authors: CW
authors: Oh
authors: Department of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine;
authors: Sung Sup
authors: SS
authors: Park
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;|Department of Anatomy, Seoul National University College of Medicine, Seoul;
authors: Ji Yeoun
authors: JY
authors: Lee
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Kyu-Chang
authors: KC
authors: Wang
authors: Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine;
authors: Seung-Ki
authors: SK
authors: Kim
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D009072:Moyamoya Disease / Q000209:etiology* / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
chemical_list: C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases
keywords: IQR = interquartile range; MMS = moyamoya syndrome; MRA = MR angiography; NF-1 = neurofibromatosis Type 1; RNF213; moyamoya syndrome; neurofibromatosis Type 1; polymorphism; vascular disorders