Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21740
Title: Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.
Authors: Bar, Claire;Barcia, Giulia;Jennesson, Mélanie;Le Guyader, Gwenaël;Schneider, Amy L;Mignot, Cyril;Lesca, Gaetan;Breuillard, Delphine;Montomoli, Martino;Keren, Boris;Doummar, Diane;de Villemeur, Thierry Billette;Afenjar, Alexandra;Marey, Isabelle;Gerard, Marion;Isnard, Hervé;Poisson, Alice;Dupont, Sophie;Berquin, Patrick;Meyer, Pierre;Genevieve, David;De Saint Martin, Anne;El Chehadeh, Salima;Chelly, Jamel;Guët, Agnès;Scalais, Emmanuel;Dorison, Nathalie;Myers, Candace T;Mefford, Heather C;Howell, Katherine B;Marini, Carla;Freeman, Jeremy L;Nica, Anca;Terrone, Gaetano;Sekhara, Tayeb;Lebre, Anne-Sophie;Odent, Sylvie;Sadleir, Lynette G;Munnich, Arnold;Guerrini, Renzo;Scheffer, Ingrid E;Kabashi, Edor;Nabbout, Rima
Affiliation: The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia
Reference centre for rare epilepsies, Department of Pediatric Neurology, Hôpital Necker-Enfants Malades, Paris, France
Laboratory of Translational Research for Neurological Disorders, INSERM UMR 1163, Imagine Institute, Paris, France
Université Paris Descartes -Sorbonne Paris Cité, Imagine Institute, Paris, France
Service de Génétique, Groupe Hospitalier Necker Enfants Malades, Assistance Publique -Hôpitaux de Paris, Paris, France
Reference centre for rare developmental abnormalities CLAD-Ouest, CHU Rennes, France
CNRS UMR 6290 Institut de Génétique et Développement de Rennes IGDR, Univ Rennes, Rennes, France
Service de génétique clinique et du Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Centre de référence maladies rares anomalies du développement, CHU Montpellier
Université Montpellier et Unité Inserm, U1183, Montpellier, France
Département de Neuropédiatrie, CHU Montpellier, Montpellier, France
PhyMedExp, U1046 INSERM, UMR9214 CNRS, Montpellier, France
INSERM, U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France
Epileptology Unit and Rehabilitation Unit AP-HP, GH Pitie-Salpêtrière-Charles Foix, F-, 75013, Paris, France
Service de Génétique, Hospices Civils de Lyon, Lyon, France
Centre de Recherche en Neurosciences de Lyon, INSERM U1028, UMR CNRS 5292, Université Claude Bernard Lyon 1, Bron Cedex, France
APHP, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique; Centre de Reference Déficience Intellectuelle de Causes Rares; GRC UPMC «Déficience Intellectuelle et Autisme», Paris, France
Service de Génétique, CHU de Poitiers, BP 577, 86021, Poitiers Cedex
EA3808 - NEUVACOD Unité neurovasculaire et troubles cognitifs, Université de Poitiers, Pôle Biologie Santé
Departments of Neurology and Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia
Murdoch Children's Research Institute, Melbourne, Victoria, Australia
Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Department of Pediatrics, American Memorial Hospital, Reims, France
Reference centre for rare epilepsies, Department of Pediatric Neurology, Hôpital Necker-Enfants Malades, Paris, France
Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A Meyer Children's Hospital, University of Florence, Florence, Italy
APHP, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique; Centre de Reference Déficience Intellectuelle de Causes Rares; GRC UPMC «Déficience Intellectuelle et Autisme», Paris, France
Department of Pediatric Neurology, AP-HP, Hôpital Armand Trousseau, Paris, France
Département de génétique et embryologie médicale, Sorbonne Université, GRC n°19, pathologies Congénitales du Cervelet-LeucoDystrophies, Centre de Référence déficiences intellectuelles de causes rares, AP-HP, Hôpital Armand Trousseau, F-, 75012, Paris, France
APHP, Hôpital Pitié-Salpêtrière, Département de Génétique et de Cytogénétique; Centre de Reference Déficience Intellectuelle de Causes Rares; GRC UPMC «Déficience Intellectuelle et Autisme», Paris, France
Clinical genetics, CHU Côte de Nacre, Caen, France
28 rue de la république 69002 Lyon
GénoPsy, Reference Center for Diagnosis and Management of Genetic Psychiatric Disorders, Centre Hospitalier le Vinatier and EDR-Psy Team (Centre National de la Recherche Scientifique & Lyon 1 Claude Bernard University)
Service de Neurologie Pédiatrie, CHU Amiens-Picardie, Université de Picardie Jules Verne, Amiens France
Department of Pediatric Neurology, Strasbourg University Hospital, Strasbourg, France
Service de génétique médicale, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg
Service de pédiatrie, Hôpital Louis-Mourier, Colombes, France
Pediatric Neurology Unit, Centre Hospitalier de Luxembourg, Luxembourg
Pediatric Neurosurgery, Rothschild Foundation Hospital, Paris
Department of Pediatrics, University of Washington, Seattle, WA
Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA
Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A Meyer Children's Hospital, University of Florence, Florence, Italy
Neurology Department, Center for Clinical Research (CIC 1414), Rennes University Hospital
Department of Translational Medical Sciences, Section of Pediatrics-Child Neurology Unit, Federico II University, 80131, Naples, Italy
Department of Pediatric Neurology, C.H.I.R.E.C, Brussels, Belgium
CHU Reims, Hôpital Maison Blanche, Pôle de Biologie, Service de Génétique, Reims, F-51092, France
Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A Meyer Children's Hospital, University of Florence, Florence, Italy
Issue Date: 12-Sep-2019
EDate: 2019-09-12
Citation: Human mutation 2019; online first: 12 September
Abstract: Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the alpha subunit of the delayed-rectifier voltage-dependent potassium channel Kv 2.1. We review the 37 previously reported patients carrying 29 distinct KCNB1 variants and significantly expand the mutational spectrum describing 18 novel variants from 27 unreported patients. Most variants occur de novo and mainly consist of missense variants located on the voltage sensor and the pore domain of Kv 2.1. We also report the first inherited variant (p.Arg583*). KCNB1-related encephalopathies encompass a wide spectrum of neurodevelopmental disorders with predominant language difficulties and behavioral impairment. Eighty-five percent of patients developed epilepsies with variable syndromes and prognosis. Truncating variants in the C-terminal domain are associated with a less severe epileptic phenotype. Overall, this report provides an up-to-date review of the mutational and clinical spectrum of KCNB1, strengthening its place as a causal gene in DEEs and emphasizing the need for further functional studies to unravel the underlying mechanisms. This article is protected by copyright. All rights reserved.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21740
DOI: 10.1002/humu.23915
ORCID: 0000-0003-1489-0211
PubMed URL: 31513310
Type: Journal Article
Subjects: KCNB1
developmental and epileptic encephalopathy
epilepsy
potassium channel
Appears in Collections:Journal articles

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