Evaluation of Mutations in Patients with Early-Onset Parkinson's Disease
Project no. 21811 · Status: Kapanmış · 2020
Summary
Objective: Parkinson's Disease (PD) is the most common neurodegenerative disease after Alzheimer's Disease (AD). The etiology of the neurodegenerative process that causes PD is still not understood, and it is thought that the interaction of genetic and environmental factors may play a role. Approximately 10% of PD cases show familial characteristics. Understanding the genetic etiology of PD will lead to a better understanding of the physiopathology of the disease. Materials and Methods: Thirty clinically familial Early Onset Parkinson Disease (EOPD) diagnosed cases that examined by sequencing exons and exon-intron boundaries using targeted new generation for 10 genes known to be responsible for etiology (SNCA, LRRK2, VPS35, PARK2, PINK1, PARK7, ATP13A2, PLA2G6, FBXO7, DNAJC6) were selected. That patients were examined for large deletions and duplications of 8 genes (SNCA, PARK7, LRRK2, ATP13A2, PINK1, GCH1, PRKN, UCHL1) by MLPA method. Results: Disease-causing mutations that associated with PD were detected in 7 of 30 cases. Identified 6 of the 7 variants were previously described (PRKN: exon 2 deletion, exon 5 deletion and exon 3-4 deletion; PLA2G6: c.1705C>T; PINK1: c.1247C>T) and 1 of the 7 variants was a novel splice site mutation (PRKN: c.1083+1delG). The clinical and genetic characteristics of the cases were discussed in terms of genotype phenotype correlation. Conclusion: This study is one of the few studies in our country investigating the molecular etiology in the EOPD group. The mutations we detected in the PRKN, PLA2G6 and PINK1 genes contribute to the cases reported in the literature in terms of genotype-phenotype correlation for PD. PRKN gene mutations and especially large deletions are quite common in familial EOPD cases in our society. A study that allows screening of other family members at risk and providing genetic counseling specific to the mutation in the family; Contribution has been made to the literature by identifying disease-related variants, creating data on our society, and expanding the genetic etiology of the disease by identifying mutations in new genes. Key Words: Parkinson, Next Generation Sequencing, MLPA