2. Academic Validation
  3. NBEA: Developmental disease gene with early generalized epilepsy phenotypes

NBEA: Developmental disease gene with early generalized epilepsy phenotypes

  • Ann Neurol. 2018 Nov;84(5):788-795. doi: 10.1002/ana.25350.
Maureen S Mulhern 1,  Constance Stumpel 2,  Nicholas Stong 1,  Han G Brunner 2 3,  Louise Bier 1,  Natalie Lippa 1,  James Riviello 4,  Rob P W Rouhl 5 6 7,  Marlies Kempers 8,  Rolph Pfundt 3,  Alexander P A Stegmann 2,  Mary K Kukolich 9,  Aida Telegrafi 10,  Anna Lehman 11,  CAUSES study,  Elena Lopez-Rangel 11,  Nada Houcinat 12 13,  Magalie Barth 14,  Nicolette den Hollander 15,  Mariette J V Hoffer 15,  Sarah Weckhuysen 16 17 18,  EuroEPINOMICS-RES-MAE working group,  Jolien Roovers 16 17,  Tania Djemie 16 17 18,  Diana Barca 19,  Berten Ceulemans 20,  Dana Craiu 19,  Johannes R Lemke 21,  Christian Korff 22,  Heather C Mefford 23,  Candace T Meyers 23,  Zsuzsanna Siegler 24,  Susan M Hiatt 25,  Gregory M Cooper 25,  E Martina Bebin 26,  Lot Snijders Blok 3 27,  Hermine E Veenstra-Knol 28,  Evan H Baugh 1,  Eva H Brilstra 29,  Catharina M L Volker-Touw 29,  Ellen van Binsbergen 29,  Anya Revah-Politi 1,  Elaine Pereira 30,  Danielle McBrian 4,  Mathilde Pacault 31,  Bertrand Isidor 31,  Cedric Le Caignec 31,  Brigitte Gilbert-Dussardier 32 33,  Frederic Bilan 32 33,  Erin L Heinzen 1 34,  David B Goldstein 1,  Servi J C Stevens 2,  Tristan T Sands 1 4
Affiliations

Affiliations

  • 1 Columbia University Medical Center, Institute for Genomic Medicine, New York, NY.
  • 2 Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
  • 3 Department of Human Genetics, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
  • 4 Department of Neurology, Columbia University Department of Neurology, New York, NY.
  • 5 Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
  • 6 Academic Center for Epileptology, Kempenhaeghe/Maastricht University Medical Center, Maastricht, the Netherlands.
  • 7 School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
  • 8 Department of Clinical Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
  • 9 Cook Children's Hospital, Fort Worth, TX.
  • 10 GeneDx, Gaithersburg, MD.
  • 11 Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
  • 12 University of Burgundy-Franche-Comté, UMR1231 GAD, INSERM, Dijon, France.
  • 13 Dijon Bourgogne University Hospital Center, Rare Diseases Reference Center "Developmental Anomalies and Informational Syndromes," Genetic Center, FHU-TRANSLAD, Dijon, France.
  • 14 Department of Biochemistry and Genetics, Angers University Hospital Center, Angers, France.
  • 15 Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
  • 16 Center for Molecular Neurology, VIB, Neurogenetics Group, Antwerp, Belgium.
  • 17 Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
  • 18 Department of Neurology, University Hospital Antwerp, Antwerp, Belgium.
  • 19 Pediatric Neurology Clinic, Al Obregia Hospital, Carol Davila University of Medicine, Bucharest, Romania.
  • 20 Department of Pediatric Neurology, University Hospital Antwerp, Antwerp, Belgium.
  • 21 Institute for Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.
  • 22 Pediatric Neurology Unit, Child and Adolescent Department, University Hospitals, Geneva, Switzerland.
  • 23 Department of Pediatrics, University of Washington, Seattle, WA.
  • 24 Bethesda Children's Hospital, Department of Neurology, Budapest, Hungary.
  • 25 HudsonAlpha Institute for Biotechnology, Huntsville, AL.
  • 26 Department of Neurology, University of Alabama at Birmingham, Birmingham, AL.
  • 27 Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, the Netherlands.
  • 28 Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • 29 University Medical Center Utrecht, Department of Genetics, Utrecht, the Netherlands.
  • 30 Division of Clinical Genetics, Department of Pediatrics, New York-Presbyterian Morgan Stanley Children's Hospital, Columbia University Medical Center, New York, NY.
  • 31 Genetics Service, Nantes University Hospital Center, Nantes, France.
  • 32 Genetics Service, Poitiers University Hospital Center, Poitiers, France.
  • 33 University of Poitiers, EA3808 NEUVACOD, Poitiers, France.
  • 34 Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY.
PMID: 30269351 DOI: 10.1002/ana.25350
Abstract

NBEA is a candidate gene for autism, and de novo variants have been reported in neurodevelopmental disease (NDD) cohorts. However, NBEA has not been rigorously evaluated as a disease gene, and associated phenotypes have not been delineated. We identified 24 de novo NBEA variants in patients with NDD, establishing NBEA as an NDD gene. Most patients had epilepsy with onset in the first few years of life, often characterized by generalized seizure types, including myoclonic and atonic seizures. Our data show a broader phenotypic spectrum than previously described, including a myoclonic-astatic epilepsy-like phenotype in a subset of patients. Ann Neurol 2018;84:796-803.

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