title: [NOTCH3 gene mutations in four Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy].
abstract: OBJECTIVE
  To search for mutations in NOTCH3 gene in four Chinese families with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
  
  
  METHODS
  Four probands from four unrelated families with typical manifestations of CADASIL were studied. The 1 approximately 12 coding exons and their flanking intron sequences of NOTCH3 gene were amplified by PCR and sequenced. Some family members in the pedigree 2 and 4 were also examined for the NOTCH3 gene mutations.
  
  
  RESULTS
  Four heterozygous missense mutations were identified in the four families: the proband 1 carrying a 268C-->T mutation in exon 3, the proband 2 a 322 C-->T mutation in exon 3, the proband 3 a 328 C-->T mutation inexon 3, and the proband 4 a 1819 C-->T mutation in exon 11, which resulted in the amino acid substitutions of R90C, C108R, R110C, and R607C respectively. Among them the C108R is a novel mutation not reported previously. Additionally, some members in the pedigree 2 and 4 also harbored the same mutations with the probands.
  
  
  CONCLUSIONS
  Four heterozygous missense mutations in NOTCH3 gene have been found in four Chinese families with CADASIL. Different point mutations in NOTCH3 lead to similar phenotype of the disease. To search for mutations in NOTCH3 in related patients will help further understand and accurately diagnose the disease and perform prenatal diagnosis in CADASIL families.
authors.affiliation: Department of Neurology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Zhao-xia
authors.initials: ZX
authors.lastname: Wang
authors.forename: He
authors.initials: H
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ding-fang
authors.initials: DF
authors.lastname: Bu
authors.forename: Xiao-yuan
authors.initials: XY
authors.lastname: Niu
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yi-ning
authors.initials: YN
authors.lastname: Huang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002544:Cerebral Infarction / Q000235:genetics*; D004252:DNA Mutational Analysis; D015161:Dementia, Multi-Infarct / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch
chemical_list: C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch