GLUT1 mutations are a rare cause of familial idiopathic generalized epilepsy
| Autor: | Striano P, Weber YG, Toliat MR, Schubert J, Leu C, Chaimana R, Baulac S, Guerrero R, Leguern E, Lehesjoki AE, Polvi A, Robbiano A, Serratosa JM, Guerrini R, N?rnberg P, Sander T, Zara F, Lerche H, Marini C, EPICURE Consortium, DEL GIUDICE, ENNIO |
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| Přispěvatelé: | Striano, P, Weber, Yg, Toliat, Mr, Schubert, J, Leu, C, Chaimana, R, Baulac, S, Guerrero, R, Leguern, E, Lehesjoki, Ae, Polvi, A, Robbiano, A, Serratosa, Jm, Guerrini, R, N?rnberg, P, Sander, T, Zara, F, Lerche, H, Marini, C, Epicure, Consortium, DEL GIUDICE, Ennio |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Nonsynonymous substitution
Male Genotype Neuroimaging Biology medicine.disease_cause Idiopathic generalized epilepsy 03 medical and health sciences Epilepsy Young Adult 0302 clinical medicine Childhood absence epilepsy medicine Humans Allele Child Alleles 030304 developmental biology Genetics 0303 health sciences Mutation Glucose Transporter Type 1 medicine.disease Penetrance 3. Good health Pedigree Phenotype Child Preschool Epilepsy Generalized Female Neurology (clinical) Juvenile myoclonic epilepsy 030217 neurology & neurosurgery |
| Popis: | 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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