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

Abstract

We performed search for mutations in the LRRK2, PRKN (parkin)and SNCA (a-synuclein) genes in 359 patients of Slavonic ethnicorigin (169 men and 190 women) with Parkinsons disease, ofwhom 345 represented sporadic cases. Age at the disease onset wasfrom 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 LRRK2as well as of structural rearrangements in the PRKN and SNCAgenes it was established that in Parkinsons disease the frequencyof these mutations is 7.5% (27 patients of 359). The mutationLRRK2-G2019S was found in 1.1% of patients, parkin gene exonic rearrangements in 5.8% (including 10.7% patients with an earlyform of Parkinsons disease and 1.7% patients with a late form ofthe disease), and SNCA gene duplication in two patients. The performed analysis showed marked heterogeneity of the molecularstructure of Parkinsons disease in Russian population, whichallows 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 Parkinsons disease changes significantly the familial prognosis and requires genetic counseling in persons from thehigh risk group.

Keywords

• parkinson’s disease
• sporadic cases
• mutation analysis
• genetic heterogeneity
• genetic counseling