Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1

Détails

ID Serval
serval:BIB_5A58613CE37B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1
Périodique
Brain
Auteur(s)
Suls A., Dedeken P., Goffin K., Van Esch H., Dupont P., Cassiman D., Kempfle J., Wuttke T. V., Weber Y., Lerche H., Afawi Z., Vandenberghe W., Korczyn A. D., Berkovic S. F., Ekstein D., Kivity S., Ryvlin P., Claes L. R., Deprez L., Maljevic S., Vargas A., Van Dyck T., Goossens D., Del-Favero J., Van Laere K., De Jonghe P., Van Paesschen W.
ISSN
1460-2156 (Electronic)
ISSN-L
0006-8950
Statut éditorial
Publié
Date de publication
07/2008
Volume
131
Numéro
Pt 7
Pages
1831-44
Langue
anglais
Notes
Suls, Arvid
Dedeken, Peter
Goffin, Karolien
Van Esch, Hilde
Dupont, Patrick
Cassiman, David
Kempfle, Judith
Wuttke, Thomas V
Weber, Yvonne
Lerche, Holger
Afawi, Zaid
Vandenberghe, Wim
Korczyn, Amos D
Berkovic, Samuel F
Ekstein, Dana
Kivity, Sara
Ryvlin, Philippe
Claes, Lieve R F
Deprez, Liesbet
Maljevic, Snezana
Vargas, Alberto
Van Dyck, Tine
Goossens, Dirk
Del-Favero, Jurgen
Van Laere, Koen
De Jonghe, Peter
Van Paesschen, Wim
eng
Research Support, Non-U.S. Gov't
England
Brain. 2008 Jul;131(Pt 7):1831-44. doi: 10.1093/brain/awn113. Epub 2008 Jun 24.
Résumé
Paroxysmal exercise-induced dyskinesia (PED) can occur in isolation or in association with epilepsy, but the genetic causes and pathophysiological mechanisms are still poorly understood. We performed a clinical evaluation and genetic analysis in a five-generation family with co-occurrence of PED and epilepsy (n = 39), suggesting that this combination represents a clinical entity. Based on a whole genome linkage analysis we screened SLC2A1, encoding the glucose transporter of the blood-brain-barrier, GLUT1 and identified heterozygous missense and frameshift mutations segregating in this and three other nuclear families with a similar phenotype. PED was characterized by choreoathetosis, dystonia or both, affecting mainly the legs. Predominant epileptic seizure types were primary generalized. A median CSF/blood glucose ratio of 0.52 (normal >0.60) in the patients and a reduced glucose uptake by mutated transporters compared with the wild-type as determined in Xenopus oocytes confirmed a pathogenic role of these mutations. Functional imaging studies implicated alterations in glucose metabolism in the corticostriate pathways in the pathophysiology of PED and in the frontal lobe cortex in the pathophysiology of epileptic seizures. Three patients were successfully treated with a ketogenic diet. In conclusion, co-occurring PED and epilepsy can be due to autosomal dominant heterozygous SLC2A1 mutations, expanding the phenotypic spectrum associated with GLUT1 deficiency and providing a potential new treatment option for this clinical syndrome.
Mots-clé
Adolescent, Adult, Blood Glucose/metabolism, Chorea/complications/diagnostic imaging/diet therapy/*genetics, Chromosome Mapping, DNA Mutational Analysis/methods, Electroencephalography, Epilepsy/complications/diagnostic imaging/diet therapy/*genetics, Exercise, Female, Glucose/cerebrospinal fluid, Glucose Transporter Type 1/*genetics, Humans, Lod Score, Magnetic Resonance Imaging, Male, Middle Aged, *Mutation, Pedigree, Phenotype, Positron-Emission Tomography
Pubmed
Open Access
Oui
Création de la notice
29/11/2018 13:37
Dernière modification de la notice
20/08/2019 15:13
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