GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction (original) (raw)

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References

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Acknowledgements

We thank all the subjects and families who participated in the study. Written informed consent was obtained from parents for their children and for themselves, according to the appropriate bioethics laws and ethical committees (no. 05/78, CPP Strasbourg, Alsace 1). We thank C. Boulay, M. Lim, E. Panagiotakaki, C. Seegmuller and M.-P. Valenti-Hirsch for their valuable participation in clinical analyses, R. Lamy for expert technical assistance, F. Michel at inMAGIC (INMED Imaging Centre) and all the administrative staff at INMED. Assistance from the Biological Resource Centre, Hospices Civils (Lyon, France) and from the Banque de Génome, Hôpital de Brabois (Vandoeuvre-les-Nancy, France) was greatly appreciated. S.W. is supported by the Wellcome Trust. P.W. and A.V. are partly supported by the NIHR Oxford Biomedical Research Centre. This work was supported by ANR (Agence Nationale de la Recherche) grant EPILAND (ANR-2010-BLAN-1405 01) with EuroBiomed label, by National PHRC (Projet Hospitalier de Recherche Clinique) grant 2010 03-08 and by INSERM.

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1. Gaetan Lesca and Gabrielle Rudolf: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Genetics, University Hospitals of Lyon, Lyon, France
   Gaetan Lesca, Audrey Labalme & Damien Sanlaville
2. Claude Bernard Lyon I University, Lyon, France
   Gaetan Lesca & Damien Sanlaville
3. Centre de Recherche en Neurosciences de Lyon, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 5292, Institut National de la Santé et de la Recherche Médicale (INSERM) U1028, Lyon, France
   Gaetan Lesca, Nadia Boutry-Kryza, Philippe Ryvlin, Alexis Arzimanoglou & Damien Sanlaville
4. French Epilepsy, Language and Development (EPILAND) Network, Marseille, France
   Gaetan Lesca, Gabrielle Rudolf, Nadine Bruneau, Audrey Labalme, Nadia Boutry-Kryza, Manal Salmi, Timur Tsintsadze, Jacques Motte, Julitta de Bellescize, Anne de Saint Martin, Dorothee Ville, Philippe Ryvlin, Alexis Arzimanoglou, Edouard Hirsch, Nail Burnashev, Damien Sanlaville & Pierre Szepetowski
5. Department of Neurology, Strasbourg University Hospital, Strasbourg, France
   Gabrielle Rudolf & Edouard Hirsch
6. Strasbourg University, Strasbourg, France
   Gabrielle Rudolf & Edouard Hirsch
7. Aix-Marseille University, Marseille, France
   Nadine Bruneau, Natalia Lozovaya, Manal Salmi, Timur Tsintsadze, Vera Tsintsadze, Nail Burnashev & Pierre Szepetowski
8. INSERM UMRS 901, Marseille, France
   Nadine Bruneau, Natalia Lozovaya, Manal Salmi, Timur Tsintsadze, Vera Tsintsadze, Nail Burnashev & Pierre Szepetowski
9. Mediterranean Institute of Neurobiology (INMED), Marseille, France
   Nadine Bruneau, Natalia Lozovaya, Manal Salmi, Timur Tsintsadze, Vera Tsintsadze, Nail Burnashev & Pierre Szepetowski
10. INSERM UMRS 663, Paris Descartes University, Paris, France
    Natalia Lozovaya
11. Laboratory of Medical Genetics, University Hospitals of Lyon, Lyon, France
    Nadia Boutry-Kryza
12. Department of Clinical Neurosciences, Institute of Psychiatry, King's College London, London, UK
    Laura Addis & Deb Pal
13. Department of Pediatrics A, American Memorial Hospital, Reims, France
    Jacques Motte
14. Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
    Sukhvir Wright, Patrick Waters & Angela Vincent
15. Department of Neurology, University Hospital Pontchaillou, Rennes, France
    Anne Michel
16. Department of Neuropediatrics, Armand-Trousseau Hospital, Paris, France
    Diane Doummar
17. Department of Paediatric Neurology, Evelina Children's Hospital, London, UK
    Karine Lascelles
18. The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
    Lisa Strug
19. The University of Toronto, Toronto, Ontario, Canada
    Lisa Strug
20. Sleep and Pediatric Neurophysiology Department, Epilepsy, University Hospitals of Lyon, Lyon, France
    Julitta de Bellescize, Philippe Ryvlin & Alexis Arzimanoglou
21. William Lennox Neurology Centre, Université Catholique de Louvain, Ottignies, Belgium
    Pascal Vrielynck
22. Pediatric Department I, Strasbourg University Hospital, Strasbourg, France
    Anne de Saint Martin
23. Department of Neuropediatrics, University Hospitals of Lyon, Lyon, France
    Dorothee Ville

Authors

1. Gaetan Lesca
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2. Gabrielle Rudolf
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3. Nadine Bruneau
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4. Natalia Lozovaya
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5. Audrey Labalme
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6. Nadia Boutry-Kryza
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7. Manal Salmi
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8. Timur Tsintsadze
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9. Laura Addis
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10. Jacques Motte
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11. Sukhvir Wright
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12. Vera Tsintsadze
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13. Anne Michel
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14. Diane Doummar
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15. Karine Lascelles
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16. Lisa Strug
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17. Patrick Waters
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18. Julitta de Bellescize
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19. Pascal Vrielynck
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20. Anne de Saint Martin
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21. Dorothee Ville
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22. Philippe Ryvlin
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23. Alexis Arzimanoglou
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24. Edouard Hirsch
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25. Angela Vincent
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26. Deb Pal
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27. Nail Burnashev
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28. Damien Sanlaville
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29. Pierre Szepetowski
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Contributions

G.L. and G.R. coordinated the collection of samples and of clinical information, performed and analyzed genetic data and participated in the study design, with equal contributions. N. Bruneau supervised and carried out the synthesis of the constructs, performed the in vitro assays and the immunocytochemistry experiments and participated in cell-based electrophysiological assays and in study design. N.L., T.T., V.T. and N. Burnashev performed and designed all electrophysiological studies and related data analyses. J.M., A.M., D.D., K.L., J.d.B., P.V., A.S.M., D.V., P.R., A.A., D.P. and E.H. performed phenotyping analysis and clinical data collection. A.L., N.B.-K., M.S., L.A., L.S. and D.P. participated in genetic experiments and analyses. S.W., P.W. and A.V. performed the in vitro immunological assays. D.S. participated in the overall strategy and in genetic data analyses and supervision. P.S. was the project leader. He decided on the overall strategy, directed the follow-up of experiments, supervised data analysis and wrote the manuscript with G.L. and G.R. and with help from N. Bruneau, N.L., N. Burnashev and D.S. All authors contributed to the final version of the manuscript.

Corresponding author

Correspondence toPierre Szepetowski.

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Competing interests

A.V. and the University of Oxford hold patents and receive royalties and payments for antibody assays for the diagnosis of neurological diseases such as myasthenia gravis and different forms of autoimmune encephalitis.

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Lesca, G., Rudolf, G., Bruneau, N. et al. GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.Nat Genet 45, 1061–1066 (2013). https://doi.org/10.1038/ng.2726

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• Received: 20 November 2012
• Accepted: 18 July 2013
• Published: 11 August 2013
• Issue Date: September 2013
• DOI: https://doi.org/10.1038/ng.2726