title: The role of SLC2A1 mutations in myoclonic astatic epilepsy and absence epilepsy, and the estimated frequency of GLUT1 deficiency syndrome.
abstract: The first mutations identified in SLC2A1, encoding the glucose transporter type 1 (GLUT1) protein of the blood-brain barrier, were associated with severe epileptic encephalopathy. Recently, dominant SLC2A1 mutations were found in rare autosomal dominant families with various forms of epilepsy including early onset absence epilepsy (EOAE), myoclonic astatic epilepsy (MAE), and genetic generalized epilepsy (GGE). Our study aimed to investigate the possible role of SLC2A1 in various forms of epilepsy including MAE and absence epilepsy with early onset. We also aimed to estimate the frequency of GLUT1 deficiency syndrome in the Danish population. One hundred twenty patients with MAE, 50 patients with absence epilepsy, and 37 patients with unselected epilepsies, intellectual disability (ID), and/or various movement disorders were screened for mutations in SLC2A1. Mutations in SLC2A1 were detected in 5 (10%) of 50 patients with absence epilepsy, and in one (2.7%) of 37 patient with unselected epilepsies, ID, and/or various movement disorders. None of the 120 MAE patients harbored SLC2A1 mutations. We estimated the frequency of SLC2A1 mutations in the Danish population to be approximately 1:83,000. Our study confirmed the role of SLC2A1 mutations in absence epilepsy with early onset. However, our study failed to support the notion that SLC2A1 aberrations are a cause of MAE without associated features such as movement disorders.
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Larsen
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.
authors.forename: Katrine Marie
authors.initials: KM
authors.lastname: Johannesen
authors.affiliation: Department of Clinical Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Ek
authors.affiliation: Department of Neuropediatrics, Herlev Hospital, Herlev, Denmark.
authors.forename: Shan
authors.initials: S
authors.lastname: Tang
authors.affiliation: Neurology Unit and Neurogenetic Laboratories, Meyer Children's Hospital, Florence, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
authors.affiliation: Department of Neuropediatrics, Odense University Hospital Denmark, Odense, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Blichfeldt
authors.affiliation: Department of Neuropediatrics, Odense University Hospital Denmark, Odense, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Kibaek
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: von Spiczak
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.|INSERM U 1127, The National Scientific Research Center UMR7225, University of Pierre and Marie Curie (Paris 6) UMR 1127, The Brain and Spinal Institute, University of Sorbonne, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weckhuysen
authors.affiliation: Department of Pediatrics, Holbaek Hospital, Holbaek, Denmark.
authors.forename: Mimoza
authors.initials: M
authors.lastname: Frangu
authors.affiliation: Department of Neuropediatrics, University Medical Center Giessen and Marburg, Giessen, Germany.
authors.forename: Bernd Axel
authors.initials: BA
authors.lastname: Neubauer
authors.affiliation: Pediatric Neurology Clinic, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Uldall
authors.affiliation: Institute of Pediatric Neurology and Muscular Diseases, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal-Infant Science, Institute of G. Gaslini, University of Genova, Genova, Italy.
authors.forename: Pasquale
authors.identifier: http://orcid.org/0000-0002-6065-1476
authors.initials: P
authors.lastname: Striano
authors.affiliation: Laboratory of Neurogenetics, Department of Neurosciences, Giannina Gaslini Institute, Genova, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kleiss
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Simpson
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Hiltrud
authors.initials: H
authors.lastname: Muhle
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.|Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Marina
authors.initials: M
authors.lastname: Nikanorova
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Jepsen
authors.affiliation: Department of Cellular and Molecular Medicine, Johannsen Center for Functional Genome Research, University of Copenhagen, Wilhelm Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.affiliation: Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Stephani
authors.affiliation: Neurology Unit and Neurogenetic Laboratories, Meyer Children's Hospital, Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Department of Clinical Genetics, University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Duno
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.|Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, London, United Kingdom.
authors.forename: Helle
authors.initials: H
authors.lastname: Hjalgrim
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
authors.forename: Deb
authors.initials: D
authors.lastname: Pal
authors.affiliation: Department of Neuropediatrics, Odense University Hospital Denmark, Odense, Denmark.|Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, U.S.A.
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
authors.affiliation: Danish Epilepsy Center, Dianalund, Denmark.|Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Rikke Steensbjerre
authors.initials: RS
authors.lastname: Møller
mesh_terms: D002239:Carbohydrate Metabolism, Inborn Errors / Q000453:epidemiology* / Q000235:genetics; D002675:Child, Preschool; D003718:Denmark / Q000453:epidemiology; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D004832:Epilepsy, Absence / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics; D051272:Glucose Transporter Type 1 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D013577:Syndrome
chemical_list: D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human
keywords: Childhood neurology; Epilepsy genetics; Glucose transporter 1 deficiency syndrome