Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Mol Sci. 2021 Jul 28;22(15):8100. doi: 10.3390/ijms22158100.
In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias and atypical parkinsonism-related syndromes. Several disease-causing mutations and genetic risk factors have been unraveled, providing a deeper molecular understanding of the complex genetic architecture underlying these conditions. These disorders are difficult to accurately diagnose and categorize, thus making genetics research challenging. On one hand, dystonia is an umbrella term linked to clinically heterogeneous forms of disease including dopa-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism and dystonia-parkinsonism, often viewed as a precursor to Parkinson's disease. On the other hand, atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration, are rare in nature and represent a wide range of diverse and overlapping phenotypic variabilities, with genetic research limited by sample size availability. The current review summarizes the plethora of available genetic information for these diseases, outlining limits and future directions.
近几十年来，遗传研究已经确定了一些有前途的途径和生物学见解，这些途径和见解有助于阐明与帕金森病相关的肌张力障碍和非典型帕金森病相关综合征的病因。已经发现了一些导致疾病的突变和遗传风险因素，为这些疾病的复杂遗传结构提供了更深入的分子理解。这些疾病很难准确诊断和分类，因此遗传研究具有挑战性。一方面，肌张力障碍是一个涵盖广泛的术语，与包括多巴反应性肌张力障碍、肌阵挛性肌张力障碍、快速进展性肌张力障碍-帕金森病和肌张力障碍-帕金森病在内的多种临床异质性疾病相关，通常被视为帕金森病的前兆。另一方面，非典型帕金森病疾病，如进行性核上性麻痹、多系统萎缩和皮质基底节变性，在性质上较为罕见，代表了广泛的不同和重叠的表型变异性，遗传研究受到样本量可用性的限制。本综述总结了这些疾病的大量可用遗传信息，概述了其局限性和未来的发展方向。
