The Analysis of Genetic Markers of Muscle Dystonia

The dystonia is movement disorder characterized by involuntary twisting, repetitive movements or irregular postures. Two major etiological groups are the primary form, where dystonia is the only neurological symptom, and the secondary form, due to inherited and/or degenerative disorders other than dystonia. Genetic basis of dystonia is heterogenous. Presently, at least 20 monogenic, mostly primary, dystonias have been recognized, and disease gene has been identified in 10 of them. However, genotype-phenotype correlations are not always clear. In addition, majority of cases are polygenic, with mostly unknown susceptibility genes. Among the secondary dystonias two monogenic diseases are especially interesting: Wilson disease (ATP7B gene) and neurodegeneration with brain iron accumulation (NBIA, PANK2 gene). In this project we will analyze genetic basis of dystonia in Serbian patients, in order to establish the frequency and spectrum of gene changes in our population. Among primary forms we will perform mutation screening in DYT1, DYT5a, DYT6, DYT8, DYT11 and DYT18 genes. Genotype-phenotype correlation and identification of possible endophenotypes in unaffected mutation carriers will be one of the focuses. In secondary forms we will analyze genes ATP7B in Wilson disease and PANK2 in NBIA. In addition, gene polymorphisms will be analyzed as modifiers of mutation penetrance and expressivity in monogenic forms, and as markers of susceptibility in sporadic dystonia cases.