title: Considerations on a mutation in the NOTCH3 gene sparing a cysteine residue: a rare polymorphism rather than a CADASIL variant.
abstract: Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear. We describe a 49-year-old woman with a CADASIL-like phenotype, carrying a novel cysteine-sparing mutation in exon 29 of the NOTCH3 gene, and discuss the possible pathogenetic role of this molecular variant. Even though atypical clinical and MRI findings make a diagnosis of CADASIL unlikely in this patient, our report nevertheless underlines the intriguing genotype-phenotype relationship in NOTCH3 mutations and the importance of functional investigation to ascertain the role of new NOTCH3 mutations in CADASIL pathogenesis.
authors.affiliation: Emergency Unit, C. Mondino National Institute of Neurology Foundation, IRCCS, Pavia, Italy. anna.bersano@gmail.com
authors.forename: Anna
authors.initials: A
authors.lastname: Bersano
authors.forename: Michela
authors.initials: M
authors.lastname: Ranieri
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciammola
authors.forename: Claudia
authors.initials: C
authors.lastname: Cinnante
authors.forename: Silvia
authors.initials: S
authors.lastname: Lanfranconi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Dotti
authors.forename: Livia
authors.initials: L
authors.lastname: Candelise
authors.forename: Cinzaia
authors.initials: C
authors.lastname: Baschirotto
authors.forename: Isabella
authors.initials: I
authors.lastname: Ghione
authors.forename: Elena
authors.initials: E
authors.lastname: Ballabio
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
mesh_terms: D000818:Animals; D046589:CADASIL / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011149:Pons / Q000473:pathology; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics
chemical_list: C499374:NOTCH3 protein, human; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D003545:Cysteine