Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA.
Ann Neurol. 2010 Oct;68(4):549-53. doi: 10.1002/ana.22138.
Primary dystonia is a movement disorder characterized by sustained muscle contractions and in which dystonia is the only or predominant clinical feature. TOR1A(DYT1) and the transcription factor THAP1(DYT6) are the only genes identified thus far for primary dystonia. Using electromobility shift assays and chromatin immunoprecipitation (ChIP) quantitative polymerase chain reaction (qPCR), we demonstrate a physical interaction between THAP1 and the TOR1A promoter that is abolished by pathophysiologic mutations. Our findings provide the first evidence that causative genes for primary dystonia intersect in a common pathway and raise the possibility of developing novel therapies targeting this pathway.
原发性肌张力障碍是一种以持续性肌肉收缩为特征的运动障碍,其中肌张力障碍是唯一或主要的临床特征。到目前为止,TOR1A(DYT1)和转录因子 THAP1(DYT6)是唯一被确定为原发性肌张力障碍的基因。通过电泳迁移率变动分析和染色质免疫沉淀(ChIP)定量聚合酶链反应(qPCR),我们证明了 THAP1 和 TOR1A 启动子之间存在物理相互作用,而这种相互作用在病理生理突变时被消除。我们的研究结果首次提供了证据,表明原发性肌张力障碍的致病基因在一个共同的途径中相交,并提出了针对该途径开发新疗法的可能性。