title: [Identification of a novel NOTCH3 mutation in a family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy].
abstract: OBJECTIVE
  To analyze potential mutations of NOTCH3 gene in a Chinese family featuring cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in order to facilitate genetic counseling and prenatal diagnosis.
  
  
  METHODS
  The proband and related family members and 100 healthy controls were recruited. The NOTCH3 gene was screened for mutations by polymerase chain reaction and direct DNA sequencing. PolyPhen-2 and SIFT software were used to predict the protein function.
  
  
  RESULTS
  The proband and two affected individuals from the family were adult-onset, with main clinical manifestations including recurrent transient ischemic attacks and(or) strokes, cognitive impairment, memory decline, and depression. MRI findings suggested multiple cerebral infarcts and severe leukoencephalopathy. A novel heterozygous missense mutation c.3043T> A (p.Cys1015Ser) located in exon 19 of NOTCH3 gene was identified not only in the proband and two patients, but also in an asymptomatic relative from the family. The same mutation was detected in none of the 100 unrelated healthy controls. Function analysis suggested that this mutation can severely affect the functions of this protein. Multiple sequence alignment revealed that the mutation site was extremely conserved in various species.
  
  
  CONCLUSIONS
  A novel heterozygous Cys1015Ser mutations in exon 19 of the NOTCH3 gene probably underlies the CADASIL in this family.
authors.affiliation: Department of Neurology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R.China. sky627@163.com.
authors.forename: Yuyou
authors.initials: Y
authors.lastname: Zhu
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Yuanbo
authors.initials: Y
authors.lastname: Wu
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.forename: Bai
authors.initials: B
authors.lastname: Hu
authors.forename: Ao
authors.initials: A
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D046589:CADASIL / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch