r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2022-27-1-32-42r-n-j-264Research ArticleИССЛЕДОВАНИЯ И КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯCLINICAL RESEARCHES AND CASE REPORTSГенетическая характеристика и клинические особенности церебральной аутосомно-доминантной артериопатии c субкортикальными инфарктами и лейкоэнцефалопатией (ЦАДАСИЛ)Genetic characteristic and clinical features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)https://orcid.org/0000-0001-5705-5182ЧеребиллоК. К.CherebilloC. C.

Черебилло Карина Константиновна

Санкт-Петербург, Льва Толстого, 6–8, Россия

Saint Petersburg

k.cherebillo@mail.ruhttps://orcid.org/0000-0002-9354-8790НазаровВ. Д.NazarovV. D.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-5601-5899КирьяновЮ. М.KiryanovY. M.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-4998-3699ЛапинС. В.LapinC. V.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-3055-6507МазингА. В.MazingA. V.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-1880-3122ШулешоваН. В.ShuleshovaN. V.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0001-6831-0441МакшаковГ. С.MakshakovG. S.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-6715-8203ТотолянН. А.TotolyanN. A.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0001-7891-9883КушнирЯ. Б.KushnirY. B.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-1865-2061КупаеваА. В.CupaevaA. V.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-8955-3765ПивеньВ. Д.PivenV. D.

Санкт-Петербург

Saint Petersburg

https://orcid.org/0000-0002-2079-0439ЭмануэльВ. Л.EmanuelV. L.

Санкт-Петербург

Saint Petersburg

ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова» Минздрава РоссииРоссияFederal State Budgetary Educational Institution of Higher Education Academician I.P. Pavlov First St. Petersburg State Medical University of the Ministry of Healthcare of Russian FederationRussian FederationСанкт-Петербургское ГБУЗ «Городская Мариинская больница»РоссияSaint Petersburg City Mariinskaya HospitalRussian FederationГородской центр рассеянного склероза и других аутоиммунных заболеваний ГБУЗ «Городская клиническая больница № 31»РоссияCity Center of Multiple Sclerosis and Other Autoimmune Diseases, City Clinical Hospital №31Russian Federation2022070320222713242Copyright © Черебилло К.К., Назаров В.Д., Кирьянов Ю.М., Лапин С.В., Мазинг А.В., Шулешова Н.В., Макшаков Г.С., Тотолян Н.А., Кушнир Я.Б., Купаева А.В., Пивень В.Д., Эмануэль В.Л., 20222022Черебилло К.К., Назаров В.Д., Кирьянов Ю.М., Лапин С.В., Мазинг А.В., Шулешова Н.В., Макшаков Г.С., Тотолян Н.А., Кушнир Я.Б., Купаева А.В., Пивень В.Д., Эмануэль В.Л.Cherebillo C.C., Nazarov V.D., Kiryanov Y.M., Lapin C.V., Mazing A.V., Shuleshova N.V., Makshakov G.S., Totolyan N.A., Kushnir Y.B., Cupaeva A.V., Piven V.D., Emanuel V.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/264Введение

Введение. Церебральная аутосомно-доминантная артериопатия с субкортикальными инфарктами и лейкоэнцефалопатией (ЦАДАСИЛ) является одной из самых распространенных генетических причин болезни мелких сосудов головного мозга.

Цель исследования

Цель исследования. Изучить частоту и выраженность клинических синдромов ЦАДАСИЛ у пациентов с подтвержденной мутацией гена NOTCH3, включая изучение распространенности самих мутаций.

Материалы и методы

Материалы и методы. В исследование включены 314 пациентов с подозрением на ЦАДАСИЛ по данным анамнеза и магнитно-резонансной томографии (МРТ). Выполнено исследование аберраций гена NOTCH3 в экзонах 2–7, 11. Для 14 пациентов с мутацией гена NOTCH3 собраны и проанализированы клинические и нейровизуализационные данные.

Результаты

Результаты. Генетические аберрации в экзонах 2–7 и 11 гена NOTCH3 выявлены у 34 из 314 обследованных, что составило 11%. Самые частые аберрации локализованы в экзоне 4 (70,4%), экзонах 3 и 6 (по 8,8%) гена NOTCH3. В 14 случаях подтвержденного ЦАДАСИЛ с точечными мутациями выполнен подробный анализ клинических и инструментальных данных.

Заключение

Заключение. Возраст дебюта ЦАДАСИЛ у пациентов в российской популяции значительно варьирует. У пациентов может наблюдаться атипичное течение болезни, включающее мозжечковую атаксию и эпилепсию, без предшествующих острых нарушений мозгового кровообращения (ОНМК). МРТ-паттерн синдрома ЦАДАСИЛ у пациентов в исследованной когорте не отличается выраженным поражением наружных капсул и височных долей, очаги в спинном мозге не исключают диагноза ЦАДАСИЛ.

Introduction

Introduction. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most common genetic causes of small-vessel cerebral diseases.

Objective

Objective. The aim of our study was to examine the frequency and severity of phenotypic spectrum in patients with CADASIL, including the study of the prevalence of the NOTCH3 gene mutations in patients with suspected CADASIL.

Material and methods

Material and methods. Sanger sequencing of exons 2–7, 11 of NOTCH3 gene was conducted in 314 patients with suspected CADASIL (confirmed by anamnesis and magnetic resonance imaging (MRI)). Clinical and MRI data were collected and analyzed for 14 patients with CADASIL.

Results

Results. NOTCH3 gene aberrations in exons 2–7, 11 were detected in 34 of 314 examined patients, that is 11% of all cases. The most frequent aberrations are localized in exon 4 (70.4%), exon 3 and exon 6 (8.8%) of the NOTCH3 gene. A detailed analysis of clinical and instrumental data was conducted in 14 cases of confirmed CADASIL with pathogenic mutations.

Conclusion

Conclusion. The age of manifestation of CADASIL in the Russian population varies significantly. Patients without a previous history of TIA/stroke may have an atypical course of the disease, including cerebellar ataxia and epilepsy. MRI pattern of the CADASIL patients of the studied cohort showed no severe damage of external capsules and temporal lobes. Spinal cord lesion are not to be excluded as a CADASIL symptom.

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The authors declare that there are no conflicts of interest present.