title: Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome.
abstract: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region.
authors.affiliation: Department of Neurology (Paediatric Neurology), Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michèl A
authors.initials: MA
authors.lastname: Willemsen
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Lisenka Elm
authors.initials: LE
authors.lastname: Vissers
authors.affiliation: Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bregje W
authors.initials: BW
authors.lastname: van Bon
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sinje
authors.initials: S
authors.lastname: Geuer
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Gilissen
authors.affiliation: Children's Hospital Aschaffenburg Alzenau, Aschaffenburg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Klepper
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Kwint
authors.affiliation: Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.
authors.forename: Wilhelmina G
authors.initials: WG
authors.lastname: Leen
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Maartje
authors.initials: M
authors.lastname: Pennings
authors.affiliation: Department of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ron A
authors.initials: RA
authors.lastname: Wevers
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Joris A
authors.initials: JA
authors.lastname: Veltman
authors.affiliation: Department of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Kamsteeg
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D002239:Carbohydrate Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D002478:Cells, Cultured; D018387:Codon, Initiator / Q000235:genetics*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D009154:Mutation; D010442:Peptide Chain Initiation, Translational
chemical_list: D020121:5' Untranslated Regions; D018387:Codon, Initiator; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human