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

Research output: Contribution to journalArticle

342 Citations (Scopus)

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

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Dystonia
Parkinsonian Disorders
Nervous System
Mutation
Penetrance
Movement Disorders
Missense Mutation
Psychological Stress
Genes
Proteins
Cell Membrane
Enzymes
sodium-translocating ATPase
Dystonia 12

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

De Carvalho Aguiar, P., Sweadner, K. J., Penniston, J. T., Zaremba, J., Liu, L., Caton, M., ... 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

Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. / De Carvalho Aguiar, Patricia; Sweadner, Kathleen J.; Penniston, John T.; Zaremba, Jacek; Liu, Liu; Caton, Marsha; Linazasoro, Gurutz; Borg, Michel; Tijssen, Marina A.J.; Bressman, Susan B.; Dobyns, William B.; Brashear, Allison; Ozelius, Laurie J.

In: Neuron, Vol. 43, No. 2, 22.07.2004, p. 169-175.

Research output: Contribution to journalArticle

De Carvalho Aguiar, P, Sweadner, KJ, Penniston, JT, Zaremba, J, Liu, L, Caton, M, Linazasoro, G, Borg, M, Tijssen, MAJ, Bressman, SB, Dobyns, WB, Brashear, A & Ozelius, LJ 2004, 'Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism', Neuron, vol. 43, no. 2, pp. 169-175. https://doi.org/10.1016/j.neuron.2004.06.028
De Carvalho Aguiar P, Sweadner KJ, Penniston JT, Zaremba J, Liu L, Caton M et al. Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron. 2004 Jul 22;43(2):169-175. https://doi.org/10.1016/j.neuron.2004.06.028
De Carvalho Aguiar, Patricia ; Sweadner, Kathleen J. ; Penniston, John T. ; Zaremba, Jacek ; Liu, Liu ; Caton, Marsha ; Linazasoro, Gurutz ; Borg, Michel ; Tijssen, Marina A.J. ; Bressman, Susan B. ; Dobyns, William B. ; Brashear, Allison ; Ozelius, Laurie J. / Mutations in the Na+/K+-ATPase α3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. In: Neuron. 2004 ; Vol. 43, No. 2. pp. 169-175.
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