{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:39:17Z","timestamp":1792157957952,"version":"4.4.0"},"reference-count":31,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2016,5]]},"abstract":"\n OBJECT<\/jats:title>\n \n Moyamoya disease (MMD) is an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. In the pathogenesis of MMD, the important role of genetic factors is being elucidated, and\n RNF213<\/jats:italic>\n has recently been identified as a susceptibility gene for MMD. The aim of this retrospective study was to investigate the\n RNF213<\/jats:italic>\n genotype in patients with MMD and to determine their genotype-phenotype associations.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n The study involved 165 Korean MMD patients from 155 unrelated families who were diagnosed with MMD at a single center from 1995 to 2013. Their demographic, radiological, and clinical findings were evaluated. Direct sequencing of the major\n RNF213<\/jats:italic>\n single nucleotide polymorphisms was performed. The association of the common\n RNF213<\/jats:italic>\n variant with MMD risk was evaluated using historical controls for comparison. Correlations between\n RNF213<\/jats:italic>\n genotype and phenotype were statistically analyzed.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n The c.14429G>A (p.R4810K) variant was identified in 125 (75.8%) of 165 MMD patients. Most patients (112) were heterozygous, and 13 patients had 2 copies of the c.14429G>A variant. A novel heterozygous variant, c.12086A>G (p.Q4029R), was found in 1 additional patient. The minor allele frequency of the c.14429G>A variant was significantly higher in the MMD group (138 [41.8%] of 330 patients) than in the control group (8 [1.36%] of 588 subjects; p < 0.001). The c.14429G>A (p.R4810K) variant significantly increased the risk of MMD in Korean patients, with an OR of 52.11 (p < 0.001) compared with controls. Moreover, c.14429G>A (p.R4810K) genotypes occurred more frequently in patients with a family history of MMD. The homozygous variant was highly associated with early-onset MMD (age at onset < 5 years), cerebral infarction at diagnosis, and cognitive impairment in long-term outcome.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n The findings indicate that the c.14429G>A (p.R4810K) allele of\n RNF213<\/jats:italic>\n is strongly associated with Korean patients with MMD. The homozygous c.14429G>A (p.R4810K) variant is particularly related to early-onset MMD, severe symptomatic manifestations at diagnosis, and poor prognosis. This genotypic variant may be a useful biomarker for early-onset MMD or unstable MMD with cerebral infarction, which requires early diagnosis and revascularization treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2015.4.jns142900","type":"journal-article","created":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T10:00:00Z","timestamp":1443780000000},"page":"1221-1227","source":"Crossref","is-referenced-by-count":108,"title":["Importance of RNF213 polymorphism on clinical features and long-term outcome in moyamoya disease"],"prefix":"10.3171","volume":"124","author":[{"given":"Eun-Hee","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pediatrics;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-Sun","family":"Yum","sequence":"additional","affiliation":[{"name":"Department of Pediatrics;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Shin","family":"Ra","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Bum","family":"Park","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Sung","family":"Ahn","sequence":"additional","affiliation":[{"name":"Departments of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gu-Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Medical Genetics Clinic and Laboratory, Asan Medical Center Children\u2019s Hospital; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Woo","family":"Goo","sequence":"additional","affiliation":[{"name":"Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Sung","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Wook","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics;"},{"name":"Medical Genetics Clinic and Laboratory, Asan Medical Center Children\u2019s Hospital; and\u00a0"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns142900","series-title":"Ann Neurol","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/ana.22427","article-title":"Acute ischemic stroke in children versus young adults","volume":"70","author":"Bigi","year":"2011"},{"key":"b2-jns142900","series-title":"Am J Hum Genet","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.ajhg.2009.04.007","article-title":"Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease","volume":"84","author":"Guo","year":"2009"},{"key":"b3-jns142900","series-title":"Biochem 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