Bressman Susan B
Department of Neurology, Beth Israel Medical Center, Albert Einstein College of Medicine New York, NY 10003, USA.
Parkinsonism Relat Disord. 2007;13 Suppl 3:S347-55. doi: 10.1016/S1353-8020(08)70029-4.
The torsion dystonias encompass a broad collection of etiologic subtypes, often divided into primary and secondary classes. Over the last two decades an increasing number of genetic causes have been identified, including an important genetic cause for early-onset primary torsion dystonia (PTD): a GAG deletion in exon 5 of DYT1, a gene that encodes torsinA. Although the exact function of torsinA remains elusive, evidence suggests aberrant localization and interaction of mutated protein; this may result in an abnormal response to stress or interference with cytoskeletal events and the development of neuronal brain pathways. Identification of DYT1 has also permitted studies of both "manifesting" and "non-manifesting"DYT1 mutation carriers. These investigations have expanded our understanding of clinical expression to include psychiatric symptoms and also have enabled imaging studies of endophenotypes. Similarly, there has been progress in our understanding of the genetic underpinnings of the "dystonia-plus" syndromes: dopa-responsive dystonia (DRD), myoclonus-dystonia (M-D), and rapid-onset dystonia-parkinsonism (RDP). These advances provide a widened platform for future research.
扭转性肌张力障碍包括多种病因亚型，通常分为原发性和继发性两类。在过去二十年中，已确定了越来越多的遗传病因，包括早发性原发性扭转性肌张力障碍（PTD）的一个重要遗传病因：DYT1基因第5外显子中的一个GAG缺失，该基因编码扭转蛋白A。尽管扭转蛋白A的确切功能仍不清楚，但有证据表明突变蛋白的定位和相互作用异常；这可能导致对应激的异常反应或对细胞骨架事件以及神经元脑通路发育的干扰。DYT1的鉴定也使得对“有症状”和“无症状”DYT1突变携带者的研究成为可能。这些研究扩展了我们对临床表型的理解，将精神症状纳入其中，还使得对内表型进行影像学研究成为可能。同样，我们对“肌张力障碍叠加”综合征（多巴反应性肌张力障碍（DRD）、肌阵挛性肌张力障碍（M-D）和快速起病的肌张力障碍-帕金森综合征（RDP））的遗传基础的理解也取得了进展。这些进展为未来的研究提供了更广阔的平台。
