title: GLUT1 mutations are a rare cause of familial idiopathic generalized epilepsy.
abstract: OBJECTIVE
  The idiopathic generalized epilepsies (IGE) are the most common genetically determined epilepsies. However, the underlying genes are largely unknown. We screened the SLC2A1 gene, encoding the glucose transporter type 1 (GLUT1), for mutations in a group of 95 European patients with familial IGE.
  
  
  METHODS
  The affected individuals were examined clinically by EEG and brain imaging. The coding regions of SLC2A1 were sequenced in the index cases of all families. Wild-type and mutant transporters were expressed and functionally characterized in Xenopus laevis oocytes.
  
  
  RESULTS
  We detected a novel nonsynonymous SLC2A1 mutation (c.694C>T, p.R232C) in one IGE family. Nine family members were affected mainly by absence epilepsies with a variable age at onset, from early childhood to adulthood. Childhood absence epilepsy in one individual evolved into juvenile myoclonic epilepsy. Eight affected and 4 unaffected individuals carried the mutation, revealing a reduced penetrance of 67%. The detected mutation was not found in 846 normal control subjects. Functional analysis revealed a reduced maximum uptake velocity for glucose, whereas the affinity to glucose and the protein expression were not different in wild-type and mutant transporters.
  
  
  CONCLUSIONS
  Our study shows that GLUT1 defects are a rare cause of classic IGE. SLC2A1 screening should be considered in IGE featuring absence epilepsies with onset from early childhood to adult life, because this diagnosis may have important implications for treatment and genetic counseling.
authors.affiliation: Muscular and Neurodegenerative Diseases Unit, G. Gaslini Institute, University of Genova, Genova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Striano
authors.forename: Y G
authors.initials: YG
authors.lastname: Weber
authors.forename: M R
authors.initials: MR
authors.lastname: Toliat
authors.forename: J
authors.initials: J
authors.lastname: Schubert
authors.forename: C
authors.initials: C
authors.lastname: Leu
authors.forename: R
authors.initials: R
authors.lastname: Chaimana
authors.forename: S
authors.initials: S
authors.lastname: Baulac
authors.forename: R
authors.initials: R
authors.lastname: Guerrero
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
authors.forename: A-E
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: A
authors.initials: A
authors.lastname: Polvi
authors.forename: A
authors.initials: A
authors.lastname: Robbiano
authors.forename: J M
authors.initials: JM
authors.lastname: Serratosa
authors.forename: R
authors.initials: R
authors.lastname: Guerrini
authors.forename: P
authors.initials: P
authors.lastname: Nürnberg
authors.forename: T
authors.initials: T
authors.lastname: Sander
authors.forename: F
authors.initials: F
authors.lastname: Zara
authors.forename: H
authors.initials: H
authors.lastname: Lerche
authors.forename: C
authors.initials: C
authors.lastname: Marini
mesh_terms: D000483:Alleles; D002648:Child; D002675:Child, Preschool; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D005838:Genotype; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D059906:Neuroimaging; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human