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Lancet Neurol. 2014 May;13(5):503-14. doi: 10.1016/S1474-4422(14)70011-0.

Distinct neurological disorders with ATP1A3 mutations.

Author information

1
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.
2
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.
3
Department of Neurology, Wake Forest School of Medicine, Winston Salem, NC, USA.
4
School of Biomedical Sciences, University of Leeds, Leeds, UK.
5
Istituto di Genetica Medica, Università Cattolica S Cuore, Rome, Italy.
6
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.
7
AHC Federation of Europe and AHC Association of Iceland, Reykjavik, Iceland.
8
Division of Pediatric Neurology, Duke University, School of Medicine, Durham, NC, USA; Department of Neurobiology, Duke University, School of Medicine, Durham, NC, USA.
9
Institute of Child Health, University College London, London, UK.
10
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.
11
Department of Genetics and Genomic Sciences and Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
12
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.
13
European Network for Research on Alternating Hemiplegia (ENRAH), Brussels, Belgium.
14
Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.
15
Department of Human Genetics and Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands.
16
Department of Biomedicine, Aarhus University, Aarhus, Denmark.

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.

PMID:
24739246
PMCID:
PMC4238309
DOI:
10.1016/S1474-4422(14)70011-0
[Indexed for MEDLINE]
Free PMC Article

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