NOTCH3 gene mutations in subjects clinically suspected of CADASIL

Lorena Mosca, Raffaella Marazzi, Alfonso Ciccone, Ignazio Santilli, Anna Bersano, Valeria Sansone, Enrico Grosso, Giorgia Mandrile, Daniela Francesca Giachino, Laura Adobbati, Elisabetta Corengia, Elio Agostoni, Anna Fiumani, Salvatore Gallone, Elio Scarpini, Mario Guidotti, Roberto Sterzi, Clara Ajmone, Alessandro Marocchi, Silvana Penco

Research output: Contribution to journalArticlepeer-review


Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebrovascular disease due to mutations involving loss or gain of a cysteine residue in the NOTCH3 gene. A cluster of mutations around exons 3 and 4 was originally reported. Identification of pathogenic mutation is important for diagnostic confirmation of the disease, however genetic counselling and testing of relatives at risk is critical in mutation carriers. Methods: Mutation analysis of the NOTCH3 gene was performed through direct sequencing in 140 patients with clinical suspicion of CADASIL. Patients underwent genetic counselling pre and post testing. The 2-23 exons containing all EGF-like domains were screened. Results: 14 familial forms of the disease have been identified with 14 different causative mutations in exons 2, 3, 4, 5, 7, 10, 14, 19, 20 and 22 of the NOTCH3 gene; no pathogenetic mutations have been identified in exons 6 and 8; several genetic variations both in coding as well as in intronic regions were identified too. Conclusions: Our data confirm the importance of screening the whole EGF-like domains region of NOTCH3 gene for the molecular diagnosis of CADASIL among the Italian population too. Moreover genetic variants different from loss or gain of a cysteine residue are identified and presented.

Original languageEnglish
Pages (from-to)144-148
Number of pages5
JournalJournal of the Neurological Sciences
Issue number1-2
Publication statusPublished - Aug 15 2011


  • Genetic counselling
  • Genetic variations
  • NOTCH3
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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