The spectrum of Notch3 mutations in 28 Italian CADASIL families

J Neurol Neurosurg Psychiatry. 2005 May;76(5):736-8. doi: 10.1136/jnnp.2004.048207.

Abstract

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cause of hereditary cerebrovascular disease. It results from mutations in the Notch3 gene, a large gene with 33 exons. A cluster of mutations around exons 3 and 4 was originally reported and limited scanning of these exons was suggested for the diagnosis in most cases.

Objective: To report Notch3 mutation analysis in 28 unrelated Italian CADASIL families from central and south Italy.

Results: The highest rate of mutations was found in exon 11 (21%) and only 18% of mutations were in exon 4. This may be related to the peculiar distribution of Notch3 mutations in the regions of origin of the families.

Conclusions: The results suggest that limited scanning of exons 3 and 4 is inadvisable in CADASIL cases of Italian origin.

MeSH terms

  • CADASIL / ethnology
  • CADASIL / genetics*
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Exons / genetics
  • Genomic Library
  • Humans
  • Italien
  • Point Mutation / genetics*
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics*
  • Receptor, Notch3
  • Receptors, Cell Surface / genetics*
  • Receptors, Notch

Substances

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