title: Mutation genotypes of RNF213 gene from moyamoya patients in Taiwan.
abstract: Moyamoya disease (MMD) is a disorder characterized by stenosis of bilateral internal carotid arteries with compensatory angiogenesis of the perforating blood vessels. Familial transmission in MMD is common. Recently, mutations in human RNF213 and ACTA2 genes were identified to be responsible for MMD. The present study was to determine whether Taiwanese MMD patients carried mutations in these two genes. Of the 36 MMD patients, eleven was found to have RNF213 mutations. Direct genetic sequencing identified four different RNF213 mutations in the 11 patients from 8 families: five with a p.R4810K, one with p.A1622V, one with p.V3933M, and the other one with p.R4131C. The latter three represent novel missense mutations. No mutation in ACTA2 gene was identified. Clinically, cerebral infarction was common in patients with an RNF213 mutation (9/11). In addition, four mutant patients had developmental delay (4/11) and two had mental dysfunction (2/11). The magnetic resonance angiography of asymptomatic mutant carriers demonstrated high incidence of multiple stenosis of intracranial vessels (3/6, 50%). Since 30.6% (11/36) of Taiwanese moyamoya patients carry an RNF213 mutation and intracranial arterial stenosis was found in half of the asymptomatic mutant carriers, it is suggested that the RNF213 mutation should form part of the diagnostic workup for MMD in clinical practice.
authors.affiliation: Department of Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC; Department of Medical Genetics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Pi-Chuan
authors.initials: PC
authors.lastname: Fan
authors.affiliation: Department of Neurosurgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Kuo-Chuan
authors.initials: KC
authors.lastname: Wang
authors.affiliation: Institute for Systems Biology, Seattle, WA, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Neurology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Jinyuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan, ROC. Electronic address: mfkenator@gmail.com.
authors.forename: Meng-Fai
authors.initials: MF
authors.lastname: Kuo
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009072:Moyamoya Disease / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D012189:Retrospective Studies; D013624:Taiwan; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C517054:MIEN1 protein, human; D009363:Neoplasm Proteins
keywords: ACTA2; ICA stenosis; Moyamoya disease; Mutation frequency; RNF213; Taiwan