Weisheit Corinne E, Pappas Samuel S, Dauer William T
Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United States.
Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, United States.
Handb Clin Neurol. 2018;147:241-254. doi: 10.1016/B978-0-444-63233-3.00016-6.
Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia - a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, and selective vulnerability of distinct neuronal populations to disease mutations. Studies of genetic forms of dystonia are also illuminating the developmental dependence of disease symptoms that is typical of many forms of the disease. As understanding of monogenic forms of dystonia grows, a clearer picture will develop of the abnormal motor circuitry behind this relatively common phenomenology. This chapter focuses on the current data covering the etiology and epidemiology, clinical presentation, and pathogenesis of four monogenic forms of isolated dystonia: DYT-TOR1A, DYT-THAP1, DYT-GCH1, and DYT-GNAL.
近几十年来，人们对肌张力障碍（一种以不自主扭转和异常姿势为特征的运动障碍）的遗传学认识有了显著提高。由于缺乏明显的神经病理学特征，研究人员正在研究孤立的单基因病因，以确定这种异质性疾病的常见分子机制。来自影像学、细胞和小鼠研究的证据表明，多巴胺神经传递缺陷、转录失调以及不同神经元群体对疾病突变的选择性易感性。对肌张力障碍遗传形式的研究也揭示了许多形式的肌张力障碍所特有的疾病症状的发育依赖性。随着对单基因形式肌张力障碍的认识不断增加，这种相对常见现象背后的异常运动回路将变得更加清晰。本章重点介绍目前有关四种孤立性肌张力障碍单基因形式（DYT-TORIA、DYT-THAP1、DYT-GCH1和DYT-GNAL）的病因学、流行病学、临床表现和发病机制的数据。
