Genetic Basis of Dystonia in Turkish families

肌张力障碍是第三种最常见的运动障碍，在许多情况下，越来越多的基因突变已被确定为遗传形式的原因。该项目的总体目标是将在运动障碍方面经验丰富的临床中心和具有分子遗传学专业知识的实验室聚集在一起，确定已知基因在土耳其肌张力障碍病因学中的作用，特别是寻找新的基因，从而获得对该疾病分子发病机制的新见解。土耳其是一个血亲率高达42%的国家，这取决于该地区，这大大增加了遗传性隐性疾病的患病率，从而增加了发现新的致病遗传变异的机会。该项目将以现有的肌张力障碍患者队列为基础，这些患者大多来自土耳其的近亲家庭。详细的表型和彻底的家庭工作将提供遗传分析的基础。纯合子作图、候选基因和全外显子组测序的结合将用于鉴定假定的遗传缺陷。潜在致病基因将在散发性和家族性特发性肌张力障碍患者的大队列中进一步评估。鉴于现有的材料，极有可能鉴定出一个或几个新的肌张力障碍基因。这将进一步深入了解这种仍然是谜的运动障碍的分子发病机制。

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.