title: Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism.
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 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.
authors.affiliation: Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: de Carvalho Aguiar
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Sweadner
authors.forename: John T
authors.initials: JT
authors.lastname: Penniston
authors.forename: Jacek
authors.initials: J
authors.lastname: Zaremba
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Marsha
authors.initials: M
authors.lastname: Caton
authors.forename: Gurutz
authors.initials: G
authors.lastname: Linazasoro
authors.forename: Michel
authors.initials: M
authors.lastname: Borg
authors.forename: Marina A J
authors.initials: MA
authors.lastname: Tijssen
authors.forename: Susan B
authors.initials: SB
authors.lastname: Bressman
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Allison
authors.initials: A
authors.lastname: Brashear
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D004421:Dystonia / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008968:Molecular Conformation; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C488756:ATP1A3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase