Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism

Patricia De Carvalho Aguiar, Kathleen J. Sweadner, John T. Penniston, Jacek Zaremba, Liu Liu, Marsha Caton, Gurutz Linazasoro, Michel Borg, Marina A.J. Tijssen, Susan B. Bressman, William B. Dobyns, Allison Brashear, Laurie J. Ozelius

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358 Scopus citations

Abstract

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 α3 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.

Original languageEnglish (US)
Pages (from-to)169-175
Number of pages7
JournalNeuron
Volume43
Issue number2
DOIs
StatePublished - Jul 22 2004
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    De Carvalho Aguiar, P., Sweadner, K. J., Penniston, J. T., Zaremba, J., Liu, L., Caton, M., Linazasoro, G., Borg, M., Tijssen, M. A. J., Bressman, S. B., Dobyns, W. B., Brashear, A., & Ozelius, L. J. (2004). Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron, 43(2), 169-175. https://doi.org/10.1016/j.neuron.2004.06.028