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 journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)144-148
Number of pages5
JournalJournal of the Neurological Sciences
Volume307
Issue number1-2
DOIs
Publication statusPublished - Aug 15 2011

Fingerprint

CADASIL
Mutation
Exons
Genes
Genetic Counseling
Epidermal Growth Factor
Cysteine
Cerebrovascular Disorders
Genetic Testing

Keywords

  • CADASIL
  • Genetic counselling
  • Genetic variations
  • NOTCH3
  • Stroke

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Mosca, L., Marazzi, R., Ciccone, A., Santilli, I., Bersano, A., Sansone, V., ... Penco, S. (2011). NOTCH3 gene mutations in subjects clinically suspected of CADASIL. Journal of the Neurological Sciences, 307(1-2), 144-148. https://doi.org/10.1016/j.jns.2011.04.019

NOTCH3 gene mutations in subjects clinically suspected of CADASIL. / Mosca, Lorena; Marazzi, Raffaella; Ciccone, Alfonso; Santilli, Ignazio; Bersano, Anna; Sansone, Valeria; Grosso, Enrico; Mandrile, Giorgia; Giachino, Daniela Francesca; Adobbati, Laura; Corengia, Elisabetta; Agostoni, Elio; Fiumani, Anna; Gallone, Salvatore; Scarpini, Elio; Guidotti, Mario; Sterzi, Roberto; Ajmone, Clara; Marocchi, Alessandro; Penco, Silvana.

In: Journal of the Neurological Sciences, Vol. 307, No. 1-2, 15.08.2011, p. 144-148.

Research output: Contribution to journalArticle

Mosca, L, Marazzi, R, Ciccone, A, Santilli, I, Bersano, A, Sansone, V, Grosso, E, Mandrile, G, Giachino, DF, Adobbati, L, Corengia, E, Agostoni, E, Fiumani, A, Gallone, S, Scarpini, E, Guidotti, M, Sterzi, R, Ajmone, C, Marocchi, A & Penco, S 2011, 'NOTCH3 gene mutations in subjects clinically suspected of CADASIL', Journal of the Neurological Sciences, vol. 307, no. 1-2, pp. 144-148. https://doi.org/10.1016/j.jns.2011.04.019
Mosca, Lorena ; Marazzi, Raffaella ; Ciccone, Alfonso ; Santilli, Ignazio ; Bersano, Anna ; Sansone, Valeria ; Grosso, Enrico ; Mandrile, Giorgia ; Giachino, Daniela Francesca ; Adobbati, Laura ; Corengia, Elisabetta ; Agostoni, Elio ; Fiumani, Anna ; Gallone, Salvatore ; Scarpini, Elio ; Guidotti, Mario ; Sterzi, Roberto ; Ajmone, Clara ; Marocchi, Alessandro ; Penco, Silvana. / NOTCH3 gene mutations in subjects clinically suspected of CADASIL. In: Journal of the Neurological Sciences. 2011 ; Vol. 307, No. 1-2. pp. 144-148.
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AU - Mosca, Lorena

AU - Marazzi, Raffaella

AU - Ciccone, Alfonso

AU - Santilli, Ignazio

AU - Bersano, Anna

AU - Sansone, Valeria

AU - Grosso, Enrico

AU - Mandrile, Giorgia

AU - Giachino, Daniela Francesca

AU - Adobbati, Laura

AU - Corengia, Elisabetta

AU - Agostoni, Elio

AU - Fiumani, Anna

AU - Gallone, Salvatore

AU - Scarpini, Elio

AU - Guidotti, Mario

AU - Sterzi, Roberto

AU - Ajmone, Clara

AU - Marocchi, Alessandro

AU - Penco, Silvana

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N2 - 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.

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