TY - JOUR
T1 - NOTCH3 gene mutations in subjects clinically suspected of CADASIL
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
PY - 2011/8/15
Y1 - 2011/8/15
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.
AB - 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.
KW - CADASIL
KW - Genetic counselling
KW - Genetic variations
KW - NOTCH3
KW - Stroke
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U2 - 10.1016/j.jns.2011.04.019
DO - 10.1016/j.jns.2011.04.019
M3 - Article
C2 - 21616505
AN - SCOPUS:79959822577
VL - 307
SP - 144
EP - 148
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1-2
ER -