title: NOTCH3 gene mutations in subjects clinically suspected of CADASIL.
abstract: 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.
authors: Department of Laboratory Medicine, Medical Genetics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors: Lorena
authors: L
authors: Mosca
authors: Raffaella
authors: R
authors: Marazzi
authors: Alfonso
authors: A
authors: Ciccone
authors: Ignazio
authors: I
authors: Santilli
authors: Anna
authors: A
authors: Bersano
authors: Valeria
authors: V
authors: Sansone
authors: Enrico
authors: E
authors: Grosso
authors: Giorgia
authors: G
authors: Mandrile
authors: Daniela Francesca
authors: DF
authors: Giachino
authors: Laura
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authors: Adobbati
authors: Elisabetta
authors: E
authors: Corengia
authors: Elio
authors: E
authors: Agostoni
authors: Anna
authors: A
authors: Fiumani
authors: Salvatore
authors: S
authors: Gallone
authors: Elio
authors: E
authors: Scarpini
authors: Mario
authors: M
authors: Guidotti
authors: Roberto
authors: R
authors: Sterzi
authors: Clara
authors: C
authors: Ajmone
authors: Alessandro
authors: A
authors: Marocchi
authors: Silvana
authors: S
authors: Penco