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Title: | Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature. | Austin 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 | Date: | 2019-09-12 | Publication information: | Human Mutation 2020; 41(1): 69-80 | 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: | https://ahro.austin.org.au/austinjspui/handle/1/21740 | DOI: | 10.1002/humu.23915 | ORCID: | 0000-0003-1489-0211 | Journal: | Human mutation | PubMed URL: | 31513310 | Type: | Journal Article | Subjects: | KCNB1 developmental and epileptic encephalopathy epilepsy potassium channel |
Appears in Collections: | Journal articles |
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