ArticleNeurobiology of disease2013
Impaired surface αβγ GABA(A) receptor expression in familial epilepsy due to a GABRG2 frameshift mutation.
Article in Neurobiology of disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Phenotypic Spectrum in Individuals With PathogenicNeurology · 2025Article
- Proteostasis regulation of GABABiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- GABAJournal of neurochemistry · 2024Review
- GABRG2 mutations in genetic epilepsy with febrile seizures plus: structure, roles, and molecular genetics.Journal of translational medicine · 2024Review
- Established and emerging GABAFrontiers in pharmacology · 2024Review
- Phenotypic Spectrum and Prognosis of Epilepsy Patients WithFrontiers in molecular neuroscience · 2022Article
- Epileptic Mechanisms Shared by Alzheimer's Disease: Viewed via the Unique Lens of Genetic Epilepsy.International journal of molecular sciences · 2021Review
- Neocortex- and hippocampus-specific deletion of Gabrg2 causes temperature-dependent seizures in mice.Cell death & disease · 2021Article
- Characterization of the GABRB2-Associated Neurodevelopmental Disorders.Annals of neurology · 2021Article
- The Broad Clinical Spectrum of Epilepsies Associated With Protocadherin 19 Gene Mutation.Frontiers in neurology · 2021Review
- Differential Coassembly of α1-GABAThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Genetic and Molecular Regulation of Extrasynaptic GABA-A Receptors in the Brain: Therapeutic Insights for Epilepsy.The Journal of pharmacology and experimental therapeutics · 2018Review
- γ2 GABAFrontiers in cellular neuroscience · 2018Review
- Molecular Pathogenic Basis for GABRG2 Mutations Associated With a Spectrum of Epilepsy Syndromes, From Generalized Absence Epilepsy to Dravet Syndrome.JAMA neurology · 2016Review
- Novel GABRG2 mutations cause familial febrile seizures.Neurology. Genetics · 2015Article
- A novel GABRG2 mutation, p.R136*, in a family with GEFS+ and extended phenotypes.Neurobiology of disease · 2014Article
- Genetic epilepsy syndromes without structural brain abnormalities: clinical features and experimental models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
- Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA.Neurology · 2014Article
- Single-cell genetic expression of mutant GABAA receptors causing Human genetic epilepsy alters dendritic spine and GABAergic bouton formation in a mutation-specific manner.Frontiers in cellular neuroscience · 2014Article
- Expanding the phenotypic spectrum of GABRG2 variants: a recurrent GABRG2 missense variant associated with a severe phenotype.Journal of neurogeneticsArticle
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The purpose of the study was to explore the pathogenic mechanisms underlying generalized epilepsy and febrile seizures plus (GEFS+) in a family with a novel γ2 subunit gene (GABRG2) frameshift mutation. Four affected and one unaffected individuals carried a c.1329delC GABRG2 mutation resulting in a subunit [γ2S(S443delC)] with a modified and elongated carboxy-terminus that is different from that of the wildtype γ2S subunit. We expressed the wildtype γ2S subunit and the predicted mutant γ2S(S443delC) subunit cDNAs in HEK293T cells and performed immunoblotting, flow cytometry and electrophysiology studies. The mutant subunit was translated as a stable protein that was larger than the wildtype γ2S subunit and was retained in the ER and not expressed on the cell surface membrane, suggesting GABRG2 haploinsufficiency. Peak GABA-evoked currents recorded from cells cotransfected with wildtype α1 and β2 subunits and mutant γ2S subunits were significantly decreased and were comparable to α1β2 receptor currents. S443delC is the first GABR epilepsy mutation predicted to abolish the natural stop codon and produce a stop codon in the 3' UTR that leads to translation of an extended peptide. The GEFS+ phenotype observed in this family is likely caused by γ2S subunit loss-of-function and possibly to dominant-negative suppression of α1β2γ2 receptors. Many GABRG2 truncation mutations result in GEFS+, but the spectrum of phenotypic severity is wider, ranging from asymptomatic individuals to the Dravet syndrome. Mechanisms influencing the severity of the phenotype are therefore complex and difficult to correlate with its demonstrable functional effects.
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Registered trials
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