title: Distinct neurological disorders with ATP1A3 mutations.
abstract: 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.
authors.affiliation: 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. Electronic address: e.heinzen@duke.edu.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Heinzen
authors.affiliation: 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.
authors.forename: Alexis
authors.initials: A
authors.lastname: Arzimanoglou
authors.affiliation: Department of Neurology, Wake Forest School of Medicine, Winston Salem, NC, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Brashear
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.affiliation: Istituto di Genetica Medica, Università Cattolica S Cuore, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gurrieri
authors.affiliation: Center for Human Genome Variation, Duke University, School of Medicine, Durham, NC, USA; Department of Molecular Genetics and Microbiology, Duke University, School of Medicine, Durham, NC, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
authors.affiliation: AHC Federation of Europe and AHC Association of Iceland, Reykjavik, Iceland.
authors.forename: Sigurður H
authors.initials: SH
authors.lastname: Jóhannesson
authors.affiliation: Division of Pediatric Neurology, Duke University, School of Medicine, Durham, NC, USA; Department of Neurobiology, Duke University, School of Medicine, Durham, NC, USA.
authors.forename: Mohamad A
authors.initials: MA
authors.lastname: Mikati
authors.affiliation: Institute of Child Health, University College London, London, UK.
authors.forename: Brian
authors.initials: B
authors.lastname: Neville
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U975, Centre de Recherche de l'Institut du Cerveau et de la Moelle, Paris, France; Centre National de la Recherche Scientifique, UMR7225, Paris, France; Université Pierre et Marie Curie Paris VI, UMRS975, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Nicole
authors.affiliation: Department of Genetics and Genomic Sciences and Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Ozelius
authors.affiliation: Danish Research Institute for Translational Neuroscience, Nordic-EMBL Partnership of Molecular Medicine, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark; Centre for Membrane Pumps in Cells and Disease-PUMPKIN, Danish National Research Foundation, Aarhus, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Poulsen
authors.affiliation: European Network for Research on Alternating Hemiplegia (ENRAH), Brussels, Belgium.
authors.forename: Tsveta
authors.initials: T
authors.lastname: Schyns
authors.affiliation: Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Sweadner
authors.affiliation: Department of Human Genetics and Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands.
authors.forename: Arn
authors.initials: A
authors.lastname: van den Maagdenberg
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Vilsen
mesh_terms: D000818:Animals; D016206:Databases, Bibliographic / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006429:Hemiplegia / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000378:metabolism
chemical_list: C488756:ATP1A3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
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