Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel C82R mutation in the NOTCH3 gene

J Alzheimers Dis. 2015;43(2):363-7. doi: 10.3233/JAD-141218.

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited cerebrovascular disease associated with mutations in the NOTCH3 gene on chromosome 19, and represents the most common hereditary stroke disorder. We describe a pedigree, which suffered the classical clinical CADASIL pattern of migraine headaches, recurrent subcortical infarcts, and subcortical dementia, associated with a previously undescribed missense mutation (c.[244T>C], p.[C82R]) in NOTCH3. This new mutation extends the list of known pathogenic mutations responsible for CADASIL, which are associated with an odd number of cysteine residues within any of the epidermal growth factor-like repeats of Notch3 receptor protein.

Keywords: C82R; CADASIL; NOTCH3 mutation; Notch3 receptor protein; dementia; headache; migraine; stroke.

MeSH terms

  • Aged
  • Arginine / genetics*
  • Brain / pathology
  • CADASIL / genetics*
  • CADASIL / pathology
  • Cysteine / genetics*
  • Family Health
  • Female
  • Genetic Association Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Receptor, Notch3
  • Receptors, Notch / genetics*

Substances

  • NOTCH3 protein, human
  • Receptor, Notch3
  • Receptors, Notch
  • Arginine
  • Cysteine