Гетерогенность спорадической болезни Паркинсона: молекулярный подход к решению проблемы

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.