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Article: First genetic evidence of GABAA receptor dysfunction in epilepsy: A mutation in the γ2-subunit gene

TitleFirst genetic evidence of GABAA receptor dysfunction in epilepsy: A mutation in the γ2-subunit gene
Authors
KeywordsSpecies Index: Xenopus Laevis
Issue Date2001
PublisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.com
Citation
Nature Genetics, 2001, v. 28 n. 1, p. 46-48 How to Cite?
AbstractMajor advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively1-6. Disruption of GABAergic neurotransmission mediated by γ-aminobutyric acid (GABA) has been implicated in epilepsy for many decades7. We now report a K289M mutation in the GABAA receptor γ2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes1,2. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABAA receptor is directly involved in human idiopathic epilepsy.
Persistent Identifierhttp://hdl.handle.net/10722/132716
ISSN
2015 Impact Factor: 31.616
2015 SCImago Journal Rankings: 23.762
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorBaulac, Sen_HK
dc.contributor.authorHuberfeld, Gen_HK
dc.contributor.authorGourfinkelAn, Ien_HK
dc.contributor.authorMitropoulou, Gen_HK
dc.contributor.authorBeranger, Aen_HK
dc.contributor.authorPrud'homme, JFen_HK
dc.contributor.authorBaulac, Men_HK
dc.contributor.authorBrice, Aen_HK
dc.contributor.authorBruzzone, Ren_HK
dc.contributor.authorLeGuern, Een_HK
dc.date.accessioned2011-03-28T09:28:30Z-
dc.date.available2011-03-28T09:28:30Z-
dc.date.issued2001en_HK
dc.identifier.citationNature Genetics, 2001, v. 28 n. 1, p. 46-48en_HK
dc.identifier.issn1061-4036en_HK
dc.identifier.urihttp://hdl.handle.net/10722/132716-
dc.description.abstractMajor advances in the identification of genes implicated in idiopathic epilepsy have been made. Generalized epilepsy with febrile seizures plus (GEFS+), benign familial neonatal convulsions and nocturnal frontal lobe epilepsy, three autosomal dominant idiopathic epilepsies, result from mutations affecting voltage-gated sodium and potassium channels, and nicotinic acetylcholine receptors, respectively1-6. Disruption of GABAergic neurotransmission mediated by γ-aminobutyric acid (GABA) has been implicated in epilepsy for many decades7. We now report a K289M mutation in the GABAA receptor γ2-subunit gene (GABRG2) that segregates in a family with a phenotype closely related to GEFS+ (ref. 8), an autosomal dominant disorder associating febrile seizures and generalized epilepsy previously linked to mutations in sodium channel genes1,2. The K289M mutation affects a highly conserved residue located in the extracellular loop between transmembrane segments M2 and M3. Analysis of the mutated and wild-type alleles in Xenopus laevis oocytes confirmed the predicted effect of the mutation, a decrease in the amplitude of GABA-activated currents. We thus provide the first genetic evidence that a GABAA receptor is directly involved in human idiopathic epilepsy.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.genetics.nature.comen_HK
dc.relation.ispartofNature Geneticsen_HK
dc.subjectSpecies Index: Xenopus Laevisen_US
dc.titleFirst genetic evidence of GABAA receptor dysfunction in epilepsy: A mutation in the γ2-subunit geneen_HK
dc.typeArticleen_HK
dc.identifier.emailBruzzone, R: bruzzone@hkucc.hku.hken_HK
dc.identifier.authorityBruzzone, R=rp01442en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/88254en_HK
dc.identifier.pmid11326274-
dc.identifier.scopuseid_2-s2.0-0035030766en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035030766&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume28en_HK
dc.identifier.issue1en_HK
dc.identifier.spage46en_HK
dc.identifier.epage48en_HK
dc.identifier.isiWOS:000168413300014-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridBaulac, S=6602469838en_HK
dc.identifier.scopusauthoridHuberfeld, G=10440613000en_HK
dc.identifier.scopusauthoridGourfinkelAn, I=6603173006en_HK
dc.identifier.scopusauthoridMitropoulou, G=8772857700en_HK
dc.identifier.scopusauthoridBeranger, A=22943106300en_HK
dc.identifier.scopusauthoridPrud'homme, JF=7007093886en_HK
dc.identifier.scopusauthoridBaulac, M=26642898200en_HK
dc.identifier.scopusauthoridBrice, A=7102675554en_HK
dc.identifier.scopusauthoridBruzzone, R=7006793327en_HK
dc.identifier.scopusauthoridLeGuern, E=7006086128en_HK
dc.identifier.citeulike3892044-

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