Evaluation of genetic and phenotypical features of hereditary parkinson's disease

Introduction and Objective: It is known that Parkinson's disease (PD) is highly idiopathic. Recently, with the advances in the field of genetics, the genetic infrastructure, which is the dark side of the disease, has started to be enlightened. It is thought that knowing the genetic mechanisms that cause the disease will provide a better understanding of the pathophysiology of the disease. Since consanguineous marriage is common in our country, it is known that genetic characteristics play a major role in the development of the disease. There are few studies in this field in our country before. In our study, it was aimed to evaluate patients who were thought to have hereditary PD and who had causative gene mutations as a result of molecular examinations, to identify common mutations in our society and to reveal their similar or different aspects with the literature. Method: In this study, molecular analysis was performed by determining 75 patients from 72 different families who were followed up with a diagnosis of PD in our clinic, who met the criteria of early onset age, having a family history of consanguineous marriage or having a patient with a similar clinic. 8 large genes associated with PD and 33 genes with Next Generation Sequencing (NGS) were studied in blood samples taken from patients by the MLPA method. The clinical characteristics of the patients with mutations were examined in detail, and HBC-UPDRS was applied to the patients during their on periods. In addition, Standardized Minimental Test (SMMT) for cognitive evaluation and Beck Depression Scale tests for depression screening were performed. Findings: In our study, mutations were found in 26 (34.8%) of 75 patients who were evaluated. Parkin gene mutation was detected in 13 (17.3%) patients, SNCA in 3 (4%), FBXO7 in 2 (2.7%) and DJ1 gene mutation in 1 patient (1.3%). In addition, heterozygous GBA gene mutation was found in 5 patients (6.7%), heterozygous Parkin mutation in one patient, and heterozygous Parkin and heterozygous LRRK2 mutation in one patient. 5 different point mutations, 4 large deletion mutations and 2 different compound heterozygous mutations were found in the parkin gene. The homozygous exon 4 c.491_491delT (V164Dfs * 13) mutation detected in 2 patients from the same family has not been previously reported. Exon 1-6 duplication in the synuclein gene, homozygous (exon 9; c.1492C> T) p.R498 * and homozygous (exon 1; c.101T> G) p.L34R mutations in the FBXO7 gene, homozygous exons 1-5 deletion in the DJ1 gene were detected. Heterozygous p.H294Q, p.R434P, p.D448H, p.G241R and p.N227K mutations in the glucocerebrosidase gene, heterozygous exon 2 deletion in the Parkin gene and heterozygous c.5178A>G(rs200185983; p.Ala1726=) mutation in the LRRK2 gene were detected. Discussion: Parkin gene mutations are the most common genetic cause of autosomal recessive PD in the world. Similarly, Parkin gene mutation is the most common mutation in our study. Since consanguineous marriage is common in our country, gene mutations with autosomal recessive (OR) inheritance were found more frequently in our study, but it should be kept in mind that rare mutations (with incomplete penetrance) can be detected, such as in the autosomal dominant (OD) inherited SNCA gene. This study draws attention to the frequent occurrence and importance of genetic factors in Parkinson's disease in our country.