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New mutations in the NOTCH3 gene in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL)статья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 7 июля 2016 г.
- Авторы: Abramycheva N., Stepanova M., Fedotova E., Klyushnikov S., Illarioshkin S., Kalashnikova L., Zakharova M., Maximova M., Tanashyan M., Lagoda O., Konovalov R., Sakharova A.
- Журнал: Journal of the Neurological Sciences
- Том: 349
- Год издания: 2014
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 196
- Последняя страница: 201
- DOI: 10.1016/j.jns.2015.01.018
- Аннотация: Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a cerebrovascular small-vessel disease caused by stereotyped mutations in the Notch3 gene altering the number of cysteine residues. Methods We directly sequenced exons 2–23 of the Notch3 gene in 30 unrelated Russian patients with clinical/neuroimaging picture suggestive of CADASIL. To confirm the pathogenicity of new nucleotide variants, we used the standard bioinformatics tools and screened 200 ethnically matched individuals as controls. Results We identified 16 different point mutations in the Notch3 gene in 18 unrelated patients, including 4 new missense mutations (C194G, V252M, C338F, and C484G). All but two mutations affected the cysteine residue. The non-cysteine change V322M was shown to be associated with CADASIL-specific deposits of granular osmiophilic material in the vascular smooth-muscle cells, which confirmed the pathogenicity of this Notch3 variant. Two patients were shown to be compound-heterozygotes carrying two pathogenic Notch3 mutations. The disease was characterized by marked clinical variability, without evident phenotype-genotype correlations. Conclusions In our sample, 60% of Russian patients with ‘clinically suspected’ CADASIL received the definitive molecularly proven diagnosis. Careful assessment of genealogical, clinical, and neuroimaging data in patients with lacunar stroke can help selecting patients with a high probability of finding mutations on genetic screening.
- Добавил в систему: Клюшников Сергей Анатольевич