Heterogeneity of sporadic Parkinson’s disease: molecular approach to solving the problem

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Abstract

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.

About the authors

Sergey N. Illarioshkin

Research Center of Neurology

Author for correspondence.
Email: snillario@gmail.com
ORCID iD: 0000-0002-2704-6282

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

Russian Federation, Moscow

P. A. Slominsky

Institute of Molecular Genetics, Russian Academy of Sciences

Email: snillario@gmail.com
Russian Federation, Moscow

M. I. Shadrina

Institute of Molecular Genetics, Russian Academy of Sciences

Email: snillario@gmail.com
Russian Federation, Moscow

G. Kh. Bagyeva

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

T. B. Zagorovskaya

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

E. D. Markova

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

Alexey V. Karabanov

Research Center of Neurology

Email: snillario@gmail.com
ORCID iD: 0000-0002-2174-2412

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

Russian Federation, Moscow

Vsevolod V. Poleshchuk

Research Center of Neurology,

Email: snillario@gmail.com
Russian Federation, Moscow

E. V. Polevaya

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

Natalia V. Fedorova

Russian Medical Academy of Continuing Professional Education

Email: snillario@gmail.com
ORCID iD: 0000-0003-2168-2138

D. Sci. (Med.), Professor

Russian Federation, Moscow

S. A. Limborskaya

Institute of Molecular Genetics

Email: snillario@gmail.com
Russian Federation, Moscow

I. A. Ivanova-Smolenskaya

Research Center of Neurology

Email: snillario@gmail.com
Russian Federation, Moscow

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Copyright (c) 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.

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