NOTCH3 gene mutations in subjects clinically suspected of CADASIL

作者：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^*

来源：Journal of the Neurological Sciences, 2011, 307(1-2): 144-148.

DOI：10.1016/j.jns.2011.04.019

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

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.

• 出版日期2011-8-15