Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Affiliation:
      Département de neurologie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
      Sorbonne Université, Institut du Cerveau et de la Moelle épinière, Inserm U 1127, CNRS UMR 7225, F‐75013, Paris, France
      Assistance Publique–Hôpitaux de Paris, Department of Neurology, Hôpital Pitié‐Salpêtrière, F‐75013, Paris, France
      Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
      Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, F‐75006, Paris, France
      AP‐HP, Hôpital Pitié‐Salpêtrière, Médecine Nucléaire, F‐75013, Paris, France
      Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France
      Institut IMAGINE, Bioinformatics Platform, Université Paris Descartes, Paris, France
      Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France
      Laboratoire de Diagnostic Génétique, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
      Sorbonne Université, CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, LIB, F-75006, Paris, France
      AP-HP, Hôpital Pitié-Salpêtrière, Médecine Nucléaire, F-75013, Paris, France
    • Abstract:
      Background: The group of dystonia genes is expanding, and mutations of these genes have been associated with various combined dystonia syndromes. Among the latter, the cause of some dystonia parkinsonism cases remains unknown.Objective: To report patients with early-onset dystonia parkinsonism as a result of loss-of-function mutations in nuclear receptor subfamily 4 group A member 2.Methods: Phenotypic characterization and exome sequencing were carried out in 2 families.Results: The 2 patients reported here both had a history of mild intellectual disability in childhood and subsequently developed dystonia parkinsonism in early adulthood. Brain magnetic resonance imaging was normal, and DATscan suggested bilateral dopaminergic denervation. Two frameshift mutations in NR4A2 were identified: a de novo insertion (NM_006186.3; c.326dupA) in the first case and another small insertion (NM_006186.3; c.881dupA) in the second.Conclusions: NR4A2 haploinsufficiency mutations have been recently reported in neurodevelopmental phenotypes. Our findings indicate that dystonia and/or parkinsonism may appear years after initial symptoms. Mutations in NR4A2 should be considered in patients with unexplained dystonia parkinsonism. © 2020 International Parkinson and Movement Disorder Society.
    • Journal Subset:
      Biomedical; Editorial Board Reviewed; Expert Peer Reviewed; Peer Reviewed; USA
    • ISSN:
      0885-3185
    • MEDLINE Info:
      PMID: NLM31922365 NLM UID: 8610688
    • Grant Information:
      //France Parkinson/International; //Revue Neurologique/International
    • Publication Date:
      20200724
    • Publication Date:
      20200722
    • DOI:
      http://dx.doi.org/10.1002/mds.27982
    • Accession Number:
      143218326
  • Citations
    • ABNT:
      WIRTH, T. et al. Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism. Movement Disorders, [s. l.], v. 35, n. 5, p. 880–885, 2020. DOI 10.1002/mds.27982. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143218326. Acesso em: 14 ago. 2020.
    • AMA:
      Wirth T, Mariani LL, Bergant G, et al. Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism. Movement Disorders. 2020;35(5):880-885. doi:10.1002/mds.27982
    • APA:
      Wirth, T., Mariani, L. L., Bergant, G., Baulac, M., Habert, M., Drouot, N., Ollivier, E., Hodžić, A., Rudolf, G., Nitschke, P., Rudolf, G., Chelly, J., Tranchant, C., Anheim, M., Roze, E., & Habert, M.-O. (2020). Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism. Movement Disorders, 35(5), 880–885. https://doi.org/10.1002/mds.27982
    • Chicago/Turabian: Author-Date:
      Wirth, Thomas, Louise Laure Mariani, Gaber Bergant, Michel Baulac, Marie‐Odile Habert, Nathalie Drouot, Emmanuelle Ollivier, et al. 2020. “Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.” Movement Disorders 35 (5): 880–85. doi:10.1002/mds.27982.
    • Harvard:
      Wirth, T. et al. (2020) ‘Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism’, Movement Disorders, 35(5), pp. 880–885. doi: 10.1002/mds.27982.
    • Harvard: Australian:
      Wirth, T, Mariani, LL, Bergant, G, Baulac, M, Habert, M, Drouot, N, Ollivier, E, Hodžić, A, Rudolf, Gorazd, Nitschke, P, Rudolf, Gabrielle, Chelly, J, Tranchant, C, Anheim, M, Roze, E & Habert, M-O 2020, ‘Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism’, Movement Disorders, vol. 35, no. 5, pp. 880–885, viewed 14 August 2020, .
    • MLA:
      Wirth, Thomas, et al. “Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.” Movement Disorders, vol. 35, no. 5, May 2020, pp. 880–885. EBSCOhost, doi:10.1002/mds.27982.
    • Chicago/Turabian: Humanities:
      Wirth, Thomas, Louise Laure Mariani, Gaber Bergant, Michel Baulac, Marie‐Odile Habert, Nathalie Drouot, Emmanuelle Ollivier, et al. “Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism.” Movement Disorders 35, no. 5 (May 2020): 880–85. doi:10.1002/mds.27982.
    • Vancouver/ICMJE:
      Wirth T, Mariani LL, Bergant G, Baulac M, Habert M, Drouot N, et al. Loss-of-Function Mutations in NR4A2 Cause Dopa-Responsive Dystonia Parkinsonism. Movement Disorders [Internet]. 2020 May [cited 2020 Aug 14];35(5):880–5. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=143218326