Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism
Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism
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DOI：
10.1016/j.neuron.2004.06.028
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发表时间：
2004-07-22
期刊：
影响因子：
16.2
通讯作者：
Ozelius, LJ
中科院分区：
文献类型：
--
作者：
Aguiar, PD;Sweadner, KJ;Ozelius, LJ
快速起病的肌张力障碍-帕金森综合征(RDP，DYT12)是一种独特的常染色体显性遗传性运动障碍，以肌张力障碍的突然发作为特征，常伴有帕金森氏症的体征。在几个小时到几个星期内突然出现症状，通常与身体或情绪压力有关，这表明触发因素引发了神经系统损伤，导致永久性神经功能障碍。我们报告了在7个无血缘关系的RDP家系中发现了6个Na+/K+-ATPaseα3亚单位(ATP1A3)基因的错义突变。蛋白质的功能研究和结构分析表明，这些突变会损害酶的活性或稳定性。这一发现表明，在肌张力障碍和帕金森症中，Na+/K+泵是一种关键蛋白质，负责跨细胞膜的电化学梯度。
Rapid-onset dystonia-parkinsonism (RDP, DYT12) is a distinctive autosomal-dominant movement disorder with variable expressivity and reduced penetrance characterized by abrupt onset of dystonia, usually accompanied by signs of parkinsonism. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability. We report the finding of six missense mutations in the gene for the Na+/K+-ATPase alpha3 subunit (ATP1A3) in seven unrelated families with RDP. Functional studies and structural analysis of the protein suggest that these mutations impair enzyme activity or stability. This finding implicates the Na+/K+ pump, a crucial protein responsible for the electrochemical gradient across the cell membrane, in dystonia and parkinsonism.