Objective: Genetic testing of the Parkin gene in patients with Parkinson’s Disease (PD) in the East European cohort from Belarus.

Background: The diagnosis of Juvenile PD is the same as idiopathic, or typical, PD except for the age of the patient. Onset usually occurs between ages 20 and 40 years with an average age of onset in the early to mid-thirties. A group of patients who had onset before 40 is very likely to include people with genetic Parkinson’s. PARK2, the gene encoding the protein parkin, is the only gene in which pathogenic variants are known to cause Parkin type of Juvenile PD. The diagnosis of Parkin type of Juvenile PD can only be confirmed when pathogenic variants are identified on both alleles of PARK2 (i.e., the individual is homozygous for the same pathogenic allele or compound heterozygous for two different pathogenic alleles) [1]. To date, identified 30 different mutations in this gene, and over 90% of them are located in exons 2, 3, 4 and 7 (“hot” exons), R275W mutation is one of the most frequently detected in European population, N273S mutation has been previously described in one case from France [2].

Methods: Genetic analysis of DNA samples of 22 PD patients with rigidity, bradykinesia, and resting tremor; 16 of them had a family history of PD. For the study was used DNA from peripheral blood leukocytes by phenol-chloroform extraction method. To identify single-nucleotide substitutions in the gene PARK2 used the method of direct sequencing of the “hot” exons. Large exon deletions and duplications PARK2 gene was performed with the denaturing High-Performance Liquid Chromatography (dHPLC). To estimate the amount of Polymerase Chain Reaction (PCR) product was carried out a comparative analysis of the following combinations of exons: 3/7/12, 2/7/8; 3/8/10, 6/11, 4/5, 3/9, 2/3/4.

Results: Mutations PARK2 gene was found in 4 with Juvenile PD of 22 patients: 1st patient- two heterozygous single nucleotide substitutions in R275W and N273S; 2nd patient – heterozygous R275W mutation and deletion of exons 3 and 4; 3rd patient – homozygous deletion of exons 3 and 4; 4th patient – heterozygous deletion of exons 3 and 4.

Conclusions: Parkin type of Juvenile PD is rare and clinically indistinguishable from idiopathic PD. Detected deletion of PARK2 exons 3 and 4 is a possibly dominant type of mutations in East European population and may be associated with the “founder effect”.

References: 1. Choi, J. M. Analysis of PARK denes in a Korean cohort of early-onset Parkinson disease / J. M. Choi // Neurogenetics. 2008. 9:263–269. 2. Lesage, S. Rare heterozyzous parkin variants in French early-onset Parkinson disease patients and controls / S. Lesage, E. Lohmann, F. Tison // J Med Genet. 2008. 45:43–46.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/molecular-genetic-nature-of-parkinsons-disease-in-the-east-european-cohort/