Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector44410.17816/psaic444Original articlesОригинальные статьиUnknownHeterogeneity of sporadic Parkinson’s disease: molecular approach to solving the problemГетерогенность спорадической болезни Паркинсона: молекулярный подход к решению проблемыhttps://orcid.org/0000-0002-2704-6282IllarioshkinSergey N.ИллариошкинСергей Николаевич
Russian Federation

D. Sci. (Med.), Prof., Corr. Member of the Russian Academy of Sciences, Deputy Director, Head, Department for brain research

д.м.н., проф., член-корр. РАН, зам. директора по научной работе, рук. отдела исследований мозга

snillario@gmail.comSlominskyP. A.СломинскийП. A.
Russian Federation
snillario@gmail.comShadrinaM. I.ШадринаM. И.
Russian Federation
snillario@gmail.comBagyevaG. Kh.БагыеваГ. Х.
Russian Federation
snillario@gmail.comZagorovskayaT. B.ЗагоровскаяT. Б.
Russian Federation
snillario@gmail.comMarkovaE. D.МарковаE. Д.
Russian Federation
snillario@gmail.comhttps://orcid.org/0000-0002-2174-2412KarabanovAlexey V.КарабановАлексей Вячеславович
Russian Federation

Cand. Sci. (Med.), Neurologist, Research Center of Neurology

к.м.н., врач-невролог ФГБНУ НЦН

snillario@gmail.comPoleshchukVsevolod V.ПолещукВсеволод Владимирович
Russian Federation
snillario@gmail.comPolevayaE. V.ПолеваяE. В.
Russian Federation
snillario@gmail.comhttps://orcid.org/0000-0003-2168-2138FedorovaNatalia V.ФедороваНаталия Владимировна
Russian Federation

D. Sci. (Med.), Professor

д.м.н., профессор каф. неврологии

snillario@gmail.comLimborskayaS. A.ЛимборскаяС. A.
Russian Federation
snillario@gmail.comIvanova-SmolenskayaI. A.Иванова-СмоленскаяИ. A.
Russian Federation
snillario@gmail.comResearch Center of NeurologyФГБНУ «Научный центр неврологии»Institute of Molecular Genetics, Russian Academy of SciencesИнститут молекулярной генетики РАНResearch Center of Neurology,ФГБНУ «Научный центр неврологии»Russian Medical Academy of Continuing Professional EducationФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования»Institute of Molecular GeneticsИнститут молекулярной генетики РАН1403200711233107022017Copyright ©; 2007, Illarioshkin S.N., Slominsky P.A., Shadrina M.I., Bagyeva G.K., Zagorovskaya T.B., Markova E.D., Karabanov A.V., Poleshchuk V.V., Polevaya E.V., Fedorova N.V., Limborskaya S.A., Ivanova-Smolenskaya I.A.Copyright ©; 2007, Illarioshkin S.N., Slominsky P.A., Shadrina M.I., Bagyeva G.K., Zagorovskaya T.B., Markova E.D., Karabanov A.V., Poleshchuk V.V., Polevaya E.V., Fedorova N.V., Limborskaya S.A., Ivanova-Smolenskaya I.A.2007Illarioshkin S.N., Slominsky P.A., Shadrina M.I., Bagyeva G.K., Zagorovskaya T.B., Markova E.D., Karabanov A.V., Poleshchuk V.V., Polevaya E.V., Fedorova N.V., Limborskaya S.A., Ivanova-Smolenskaya I.A.Illarioshkin S.N., Slominsky P.A., Shadrina M.I., Bagyeva G.K., Zagorovskaya T.B., Markova E.D., Karabanov A.V., Poleshchuk V.V., Polevaya E.V., Fedorova N.V., Limborskaya S.A., Ivanova-Smolenskaya I.A.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/444

We performed search for mutations in the LRRK2, PRKN (parkin) and SNCA (a-synuclein) genes in 359 patients of Slavonic ethnic origin (169 men and 190 women) with Parkinson’s disease, of whom 345 represented sporadic cases. Age at the disease onset was from 23 to 84 years, and patients with juvenile parkinsonism (debut of symptoms before 20 years) were excluded from enrollment. On study of a major mutation G2019S in the gene LRRK2 as well as of structural rearrangements in the PRKN and SNCA genes it was established that in Parkinson’s disease the frequency of these mutations is 7.5% (27 patients of 359). The mutation LRRK2-G2019S was found in 1.1% of patients, parkin gene exonic rearrangements in 5.8% (including 10.7% patients with an early form of Parkinson’s disease and 1.7% patients with a late form of the disease), and SNCA gene duplication in two patients. The performed analysis showed marked heterogeneity of the molecular structure of Parkinson’s disease in Russian population, which allows to consider this disorder not to be a unified form but rathera group of separate (although similar) neurodegenerative syndromes. The identification of inherited mutations in a part of sporadic cases of Parkinson’s disease changes significantly the familial prognosis and requires genetic counseling in persons from the ‘high risk’ group.

Проведен поиск мутаций в генах PRKN (паркин), LRRK2 и SNCA (a-синуклеин) у 359 пациентов славянского этнического происхождения (169 мужчин и 190 женщин) с болезнью Паркинсона, из которых 345 представляли спорадические случаи. Возраст манифестации симптомов составил от 23 до 84 лет, пациенты с ювенильным паркинсонизмом (дебют симптомов до 20 лет) исключались из набора. При исследовании мажорной мутации G2019S в гене LRRK2, а также структурных перестроек в генах PRKN и SNCA было установлено, что при болезни Паркинсона частота изучаемых мутаций составляет 7,5% (27 больных из 359). Мутация LRRK2-G2019S выявлена у 1,1% больных, экзонные перестройки в паркине -у 5,8% (в том числе у 10,7% больных с ранней формой болезни Паркинсона и у 1,7% пациентов с поздней формой болезни), дупликация гена SNCA -у 2 больных. Проведенный анализ показал выраженную гетерогенность молекулярной структуры болезни Паркинсона в российской популяции, что позволяет считать данное заболевание не единой нозологической формой, а совокупностью самостоятельных (хотя и сходных) нейродегенеративных синдромов. Идентификация наследуемых мутаций в части спорадических случаев болезни Паркинсона существенно меняет семейный прогноз и требует проведения медико-генетического консультирования у лиц из группы высокого риска.

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