De novo mutation in the Notch3 gene causing CADASIL

Ann Neurol. 2000 Mar;47(3):388-91.


CADASIL, an autosomal dominant arteriopathy responsible for stroke and dementia, is caused by strongly stereotyped mutations in the Notch3 gene. We report a patient with a condition strongly suggestive of CADASIL (migraine, stroke, and white matter abnormalities), except that this patient did not have any first-degree relatives with similar symptoms. This patient carried a heterozygous Arg182Cys mutation in the Notch3 gene; this mutation was absent in his two biological parents. These data demonstrate the occurrence of a de novo noninherited mutation in the Notch3 gene, which indicates that CADASIL should not be rejected in the absence of a family history. Therefore, our finding suggests that CADASIL may be more frequent than anticipated.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Dementia, Multi-Infarct / genetics*
  • Dementia, Multi-Infarct / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Mutation, Missense / genetics*
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Receptor, Notch3
  • Receptors, Cell Surface*
  • Receptors, Notch
  • Skin / pathology
  • Skin / ultrastructure


  • NOTCH3 protein, human
  • Proto-Oncogene Proteins
  • Receptor, Notch3
  • Receptors, Cell Surface
  • Receptors, Notch