Genetic Basis of Dystonia in Turkish families

点击翻译按钮获取中文摘要

Dystonia is the third most common movement disorder, and mutations in a growing number of genes have been identified as causes for hereditary forms in many cases. The overall aims of the project, which brings together clinical centers experienced in movement disorders and laboratories with expertise in molecular genetics, are to define the role of known genes in the etiology of dystonia in Turkey, but especially to find new genes and therefore gain novel insight into the molecular pathogenesis of the disorder. Turkey is a country with a consanguinity rate of up to 42%, depending on the region, which greatly increases the prevalence of hereditary recessive diseases, thereby increasing the chances to find novel causative genetic variants. The project will build on an existing cohort of patients with dystonia, mostly from consanguineous families in Turkey. Detailed phenotyping and a thorough work-up of the families will provide the basis for genetic analysis. A combination of homozygosity mapping, candidate gene and whole exome sequencing will be used to identify the putative genetic defects. Genes which are potentially disease-causing will be further assessed in a large cohort of patients with sporadic and familial idiopathic dystonia. Given the available material, it is highly likely that one or several novel dystonia genes will be identified. This will provide further insight into the molecular pathogenesis of this still enigmatic movement disorder.