Center for Human Genome Variation, Duke University, School of Medicine, Durham, NC, USA; Department of Medicine, Section of Medical Genetics, Duke University, School of Medicine, Durham, NC, USA.
Epilepsy, Sleep and Pediatric Neurophysiology Department, HFME, University Hospitals of Lyon, France; Centre de Recherche en Neurosciences de Lyon, Centre National de la Recherche Scientifique, UMR 5292, INSERM U1028, Lyon, France.
Lancet Neurol. 2014 May;13(5):503-14. doi: 10.1016/S1474-4422(14)70011-0.
Genetic research has shown that mutations that modify the protein-coding sequence of ATP1A3, the gene encoding the α3 subunit of Na(+)/K(+)-ATPase, cause both rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood. These discoveries link two clinically distinct neurological diseases to the same gene, however, ATP1A3 mutations are, with one exception, disease-specific. Although the exact mechanism of how these mutations lead to disease is still unknown, much knowledge has been gained about functional consequences of ATP1A3 mutations using a range of in-vitro and animal model systems, and the role of Na(+)/K(+)-ATPases in the brain. Researchers and clinicians are attempting to further characterise neurological manifestations associated with mutations in ATP1A3, and to build on the existing molecular knowledge to understand how specific mutations can lead to different diseases.
遗传研究表明，改变钠钾-ATP 酶 α3 亚基（ATP1A3）蛋白编码序列的突变会导致快速发作性运动障碍帕金森病和儿童交替性偏瘫。这些发现将两种临床表现明显不同的神经疾病与同一个基因联系起来，然而，除了一个例外，ATP1A3 突变是疾病特异性的。尽管这些突变导致疾病的确切机制仍不清楚，但通过一系列体外和动物模型系统，以及钠钾-ATP 酶在大脑中的作用，人们已经获得了大量关于 ATP1A3 突变的功能后果的知识。研究人员和临床医生正在试图进一步描述与 ATP1A3 突变相关的神经表现，并在现有的分子知识基础上进一步理解特定突变如何导致不同的疾病。
