Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

Author:

Wolff Markus1,Johannesen Katrine M.23,Hedrich Ulrike B. S.4,Masnada Silvia5,Rubboli Guido26,Gardella Elena23,Lesca Gaetan789,Ville Dorothée10,Milh Mathieu1112,Villard Laurent12,Afenjar Alexandra13,Chantot-Bastaraud Sandra13,Mignot Cyril14,Lardennois Caroline15,Nava Caroline1617,Schwarz Niklas4,Gérard Marion18,Perrin Laurence19,Doummar Diane20,Auvin Stéphane2122,Miranda Maria J.23,Hempel Maja24,Brilstra Eva25,Knoers Nine25,Verbeek Nienke25,van Kempen Marjan25,Braun Kees P.26,Mancini Grazia27,Biskup Saskia28,Hörtnagel Konstanze28,Döcker Miriam28,Bast Thomas29,Loddenkemper Tobias30,Wong-Kisiel Lily31,Baumeister Friedrich M.32,Fazeli Walid33,Striano Pasquale34,Dilena Robertino35,Fontana Elena36,Zara Federico37,Kurlemann Gerhard38,Klepper Joerg39,Thoene Jess G.40,Arndt Daniel H.41,Deconinck Nicolas42,Schmitt-Mechelke Thomas43,Maier Oliver44,Muhle Hiltrud45,Wical Beverly46,Finetti Claudio47,Brückner Reinhard48,Pietz Joachim49,Golla Günther50,Jillella Dinesh51,Linnet Karen M.52,Charles Perrine53,Moog Ute54,Õiglane-Shlik Eve55,Mantovani John F.56,Park Kristen57,Deprez Marie58,Lederer Damien58,Mary Sandrine58,Scalais Emmanuel59,Selim Laila60,Van Coster Rudy61,Lagae Lieven62,Nikanorova Marina2,Hjalgrim Helle23,Korenke G. Christoph63,Trivisano Marina64,Specchio Nicola64,Ceulemans Berten65,Dorn Thomas66,Helbig Katherine L.67,Hardies Katia6869,Stamberger Hannah686970,de Jonghe Peter686970,Weckhuysen Sarah686970,Lemke Johannes R.71,Krägeloh-Mann Ingeborg1,Helbig Ingo4572,Kluger Gerhard7374,Lerche Holger4,Møller Rikke S23

Affiliation:

1. 1 Department of Pediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany

2. 2 The Danish Epilepsy Centre, Dianalund, Denmark

3. 3 Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark

4. 4 Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

5. 5 Department of Brain and Behavior, University of Pavia, Italy

6. 6 University of Copenhagen, Copenhagen, Denmark

7. 7 Department of Genetics, Lyon University Hospital, Lyon, France

8. 8 Claude Bernard Lyon I University, Lyon, France

9. 9 Lyon Neuroscience Research Centre, CNRS UMRS5292, INSERM U1028, Lyon, France

10. 10 Department of Pediatric Neurology and Reference Center for Rare Children Epilepsy and Tuberous Sclerosis, Hôpital Femme Mere Enfant, Centre Hospitalier Universitaire de Lyon, HCL, France

11. 11 APHM Service de neurologie pédiatrique, Marseille, France

12. 12 Aix Marseille Univ, Inserm, GMGF, UMR-S 910, Marseille, France

13. 13 AP-HP, Unité de Gènètique Clinique, Hôpital Armand Trousseau, Groupe Hospitalier Universitaire de l’Est Parisien, Paris, France

14. 14 AP-HP, Département de Génétique; Centre de Référence Défiences Intellectuelles de Causes Rares; Groupe de Recherche Clinique UPMC “Déficiences Intellectuelles et Autisme” GH Pitié-Salpêtrère, Paris, France

15. 15 Service de Pediatrie neonatale et Réanimation - Neuropediatrie, 76000 Rouen, France

16. 16 Sorbonne Universités, UPMC Univ Paris 06, UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM, France

17. 17 Department of Genetics, Pitié-Salpêtrière Hospital, AP-HP, F-75013 Paris, France

18. 18 Service de Génétique Clinique, CHU Caen, France

19. 19 Department of Genetics, Robert Debré Hospital, AP-HP, Paris, France

20. 20 AP-HP, Service de Neuropédiatrie, Hôpital Trousseau, Paris, France

21. 21 Université Paris Diderot, Sorbonne Paris Cité, INSERM UMR1141, Paris, France

22. 22 AP-HP, Hôpital Robert Debré, Service de Neurologie Pédiatrique, Paris, France

23. 23 Department of Pediatrics, Herlev University Hospital, Herlev, Denmark

24. 24 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

25. 25 Department of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands

26. 26 Department of Pediatric Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, The Netherlands

27. 27 Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands

28. 28 CeGaT - Center for Genomics and Transcriptomics, Tübingen, Germany

29. 29 Epilepsy Center Kork, Kehl, Germany

30. 30 Division of Epilepsy and Clinical Neurophysiology, Boston Children’s Hospital, Harvard Medical School, Boston MA, USA

31. 31 Division of Child and Adolescent Neurology, Department of Neurology, Mayo Clinic, Rochester MN, USA

32. 32 Children’s Hospital, RoMed Klinikum, Rosenheim, Germany

33. 33 Pediatric Neurology, University Hospital Cologne, Germany

34. 34 Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health, University of Genoa ‘G. Gaslini’ Institute, Genova, Italy

35. 35 Servizio di Epilettologia e Neurofisiopatologia Pediatrica, UO Neurofisiopatologia, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy

36. 36 Centro di Diagnosi e Cura delle Epilessie Infantili, Azienda Ospedaliera -Policlinico Gianbattista Rossi, Verona, Italy

37. 37 Laboratory of Neurogenetics and Neuroscience, Department of Neuroscience, “G. Gaslini” Institute, Genova, Italy

38. 38 Department of Pediatric Neurology, University Children’s Hospital, Münster, Germany

39. 39 Children’s Hospital, Klinikum Aschaffenburg, Germany

40. 40 University of Michigan, Pediatric Genetics, Ann Arbor, MI USA

41. 41 Division of Pediatric Neurology and Epilepsy – Beaumont Children’s Hospital, William Beaumont Oakland University School of Medicine, Royal Oak, Michigan, USA

42. 42 Department of Neurology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium

43. 43 Children’s Hospital Lucerne, Luzerner Kantonsspital, Kinderspital Luzern, CH-6000 Luzern 16, Switzerland

44. 44 Department of child neurology, Children’s Hospital, St. Gallen, Switzerland

45. 45 Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Christian-Albrechts University, Kiel, Germany

46. 46 Gillette Children’s Specialty Healthcare, Saint Paul, MN, USA

47. 47 Klinik für Kinder- und Jugendmedizin, Elisabeth-Krankenhaus, Essen, Germany

48. 48 Wangen, Germany

49. 49 Pediatric Practice University Medical Center for Children and Adolescents, Angelika Lautenschläger Children’s Hospital, Heidelberg, Germany

50. 50 Klinik für Kinder- und Jugendmedizin, Klinikum Lippe GmbH, Detmold, Germany

51. 51 Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children’s Hospital, Boston, MA, USA

52. 52 Department of Pediatrics, Aarhus University hospital, Aarhus, Denmark

53. 53 Department of Genetics and Cytogenetics, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière Charles-Foix, Paris, France

54. 54 Institute of Genetics, University Hospital, Heidelberg, Germany

55. 55 Children’s Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

56. 56 Department of Pediatrics and Mercy Kids Autism Center, Mercy Children’s Hospital, St. Louis, Missouri, USA

57. 57 Department of Pediatrics and Neurology, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA

58. 58 Centre de Génétique Humaine, Institut de Pathologie et Génétique, Gosselies, Belgium

59. 59 Pediatric Neurology Unit, Pediatric Department, Centre Hospitalier de Luxembourg, Luxembourg

60. 60 Department of Pediatrics, Pediatric Neurology and Neurometabolic Unit, Cairo University Children Hospital, Cairo, Egypt

61. 61 Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium

62. 62 Department of Development and Regeneration, Section Pediatric Neurology, University Hospital KU Leuven, Leuven, Belgium

63. 63 Zentrum für Kinder- und Jugendmedizin (Elisabeth Kinderkrankenhaus), Klinik für Neuropädiatrie u. Angeborene, Stoffwechselerkrankungen, Oldenburg, Germany

64. 64 Neurology Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

65. 65 Paediatric Neurology University Hospital and University of Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium

66. 66 Swiss Epilepsy Center, Zurich, Switzerland

67. 67 Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, California, USA

68. 68 Neurogenetics Group, Center for Molecular Neurology, VIB, Antwerp, Belgium

69. 69 Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium

70. 70 Division of Neurology, University Hospital Antwerp (UZA), Antwerp, Belgium

71. 71 Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany

72. 72 Division of Neurology, The Children’s Hospital of Philadelphia, Philadelphia, USA

73. 73 Neuropediatric Clinic and Clinic for Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schoen Klinik, Vogtareuth, Germany

74. 74 PMU Salzburg, Austria

Funder

German Research Foundation

German Ministry for Education and Research

German chapter of the International League Against Epilepsy (DGfE)

EU FP7 project EpiPGX

European Science Foundation

German Ministry for Education and Research (BMBF)

ESF/Euro-Epinomics

Fund for Scientific Research Flanders

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

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