NBEA : Developmental disease gene with early generalized epilepsy phenotypes

Maureen Mulhern (1) , Constance Stumpel (2) , Nicholas Stong (1) , Han Brunner (2) , Louise Bier (1) , Natalie Lippa (1) , James Riviello , Rob Rouhl (2) , Marlies Kempers (3) , Rolph Pfundt (4) , Alexander Stegmann (2) , Mary Kukolich , Aida Telegrafi (5) , Anna Lehman , Elena Lopez-Rangel , Nada Houcinat (6, 7, 8) , Magalie Barth (9) , Nicolettè den Hollander (10) , Mariette Hoffer , Sarah Weckhuysen (11) , Jolien Roovers , Tania Djemie (12) , Diana Barca , Berten Ceulemans (12) , Dana Craiu (13) , Johannes Lemke , Christian Korff (14) , Heather Mefford , Candace Meyers , Zsuzsanna Siegler , Susan Hiatt , Gregory Cooper , E. Martina Bebin , Lot Snijders Blok (3) , Hermine Veenstra-Knol , Evan Baugh , Eva Brilstra (15) , Catharina Volker-Touw , Ellen van Binsbergen (16) , Anya Revah-Politi , Elaine Pereira , Danielle Mcbrian , Mathilde Pacault (17) , Bertrand Isidor (18) , Cédric Le Caignec (19) , Brigitte Gilbert-Dussardier , Frédéric Bilan , Erin Heinzen , David Goldstein , Servi Stevens , Tristan Sands (1)

1 CUMC - Columbia University Medical Center
2 MUMC - Maastricht University Medical Centre
3 Radboud University Medical Center [Nijmegen]
4 Donders Institute for Brain, Cognition and Behaviour
5 GeneDx [Gaithersburg, MD, USA]
6 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
7 Equipe GAD (LNC - U1231)
8 UBFC - Université Bourgogne Franche-Comté [COMUE]
9 Service de génétique [Angers]
10 Department of Human Genetics
11 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
12 UA - University of Antwerp
13 UMPCD - University of Medicine and Pharmacy “Carol Davila” Bucharest
14 Dpt de l'Enfant et de l'Adolescent, Neuropédiatrie [Genève]
15 University Medical Center [Utrecht]
16 Department of Medical Genetics
17 Department of Medicine
18 Service de génétique médicale - Unité de génétique clinique [Nantes]
19 CHU Nantes - Centre Hospitalier Universitaire de Nantes

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.

Mots clés: NBEA encodes neurobeachin; De-Novo Mutations; Neurobeachin; Autism; Framework; Spectrum; Deletion; Patient

Domaines: Génétique humaine

Maureen Mulhern, Constance Stumpel, Nicholas Stong, Han Brunner, Louise Bier, et al.. NBEA : Developmental disease gene with early generalized epilepsy phenotypes. Annals of Neurology, 2018, 84 (5), pp.788-795. ⟨10.1002/ana.25350⟩. ⟨hal-02061923⟩