title: Screening for NOTCH3 gene mutations among 151 consecutive Korean patients with acute ischemic stroke.
abstract: BACKGROUND
  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disorder of cerebral small blood vessels caused by mutations in the NOTCH3 gene. The initial detection of CADASIL may be more difficult among Asian populations because common clinical phenotypes and neuroimaging findings are not frequently found in these populations. The purpose of this study was to screen the NOTCH3 gene for mutations among consecutive patients with acute ischemic stroke from our region in Korea.
  
  
  METHODS
  Between April 2008 and March 2009, 151 consecutive patients with acute ischemic stroke were screened for NOTCH3 mutations. All patients underwent a detailed clinical examination and structured interview for clinical symptoms and family history. We reviewed brain magnetic resonance imaging data from stroke patients to assess the severity of white-matter hyperintensity lesions, the number of cerebral microbleeds, and the number of lacunar infarctions. Polymerase chain reaction was used to screen exons 3, 4, 6, 11, and 18 of the NOTCH3 gene.
  
  
  RESULTS
  Among 151 consecutive patients with acute ischemic stroke, 6 patients (4.0%; 95% confidence interval [CI] 0.9-7.1) possessed a NOTCH3 gene mutation. All patients exhibited the same R544C mutation in exon 11. Four of these 6 patients presented with large artery atherosclerosis. The prevalence of CADASIL in patients with neuroimaging features consistent with advanced small-vessel disease was 36.0% (95% CI 8.0-64.8).
  
  
  CONCLUSIONS
  In this region, NOTCH3 gene mutations are frequently found in acute stroke patients who present with neuroimaging features consistent with advanced small-vessel disease.
authors: Department of Neurology, Jeju National University, Jeju, Korea. strokedoc.choi@gmail.com
authors: Jay Chol
authors: JC
authors: Choi
authors: Keun-Hwa
authors: KH
authors: Lee
authors: Sook-Keun
authors: SK
authors: Song
authors: Jung Seok
authors: JS
authors: Lee
authors: Sa-Yoon
authors: SY
authors: Kang
authors: Ji-Hoon
authors: JH
authors: Kang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002545:Brain Ischemia / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D046589:CADASIL / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D056910:Republic of Korea / Q000453:epidemiology; D020521:Stroke / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch