title: Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese.
abstract: OBJECTIVE
  Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan.
  
  
  METHODS
  Mutational analysis of NOTCH3 exons 2 to 23 by direct nucleotide sequencing was performed in patients with clinically suspected CADASIL. MRI findings were retrospectively evaluated and scored using a modified Schelten's scale.
  
  
  RESULTS
  Nine different point mutations of NOTCH3 were identified in 21 unrelated patients. Intriguingly, 47.6 % were in exon 11, and 19 % in each of exon 4 and 18. R544C was very common and present in all patients with a mutation in exon 11. Many patients with NOTCH3 R544C share the same haplotype linked to the mutation using markers D19S929 and D19S411, which flank the NOTCH3. The sensitivity of T2-weighted MRI detecting anterior temporal abnormality was only 42.9 %. Furthermore, the neuroimaging evidence of intracerebral hemorrhage (ICH) was present in 23.8 % of the 21 patients.
  
  
  CONCLUSIONS
  A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.
authors.affiliation: Dept. of Neurology, National Yang-Ming University, School of Medicine, #155, Sec.2, Li-nung St., Peitou District, Taipei, Taiwan 112, Republic of China.
authors.forename: Yi-Chung
authors.initials: YC
authors.lastname: Lee
authors.forename: Chin-San
authors.initials: CS
authors.lastname: Liu
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chang
authors.forename: Kon-Ping
authors.initials: KP
authors.lastname: Lin
authors.forename: Jong-Ling
authors.initials: JL
authors.lastname: Fuh
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Lu
authors.forename: Ya-Fen
authors.initials: YF
authors.lastname: Liu
authors.forename: Bing-Wen
authors.initials: BW
authors.lastname: Soong
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D046589:CADASIL / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D013624:Taiwan
chemical_list: D005819:Genetic Markers; C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch