Rare variants in the GABA
GABA receptor type A subunit epsilon
GABRE
exome sequencing
genetic epilepsy
novel sequence variants
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
21
02
2020
revised:
29
05
2020
accepted:
31
05
2020
pubmed:
27
6
2020
medline:
28
5
2021
entrez:
27
6
2020
Statut:
ppublish
Résumé
Epilepsy belongs to a group of chronic and highly heterogeneous brain disorders. Many types of epilepsy and epileptic syndromes are caused by genetic factors. The neural amino acid y-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system. It regulates activity of channel pores by binding to transmembrane GABA-receptors (GABRs). The GABRs are heteropentamers assembled from different receptor subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3). Several epileptic disorders are caused by mutations in genes encoding single GABRs. We applied trio- and single-whole exome sequencing to search for genetic sequence variants associated with a wide range of epileptic phenotypes accompanied by intellectual disability and/or global developmental delay in the investigated patients. We identified four hemizygous sequence variants in the GABA Our clinical and molecular genetic findings suggest that GABRE is a likely candidate gene for epilepsy. Nevertheless, functional studies are necessary to better understand pathogenicity of the GABRE-mutations and their associations with epileptic phenotypes.
Sections du résumé
BACKGROUND
Epilepsy belongs to a group of chronic and highly heterogeneous brain disorders. Many types of epilepsy and epileptic syndromes are caused by genetic factors. The neural amino acid y-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the mammalian central nervous system. It regulates activity of channel pores by binding to transmembrane GABA-receptors (GABRs). The GABRs are heteropentamers assembled from different receptor subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3). Several epileptic disorders are caused by mutations in genes encoding single GABRs.
METHODS
We applied trio- and single-whole exome sequencing to search for genetic sequence variants associated with a wide range of epileptic phenotypes accompanied by intellectual disability and/or global developmental delay in the investigated patients.
RESULTS
We identified four hemizygous sequence variants in the GABA
CONCLUSION
Our clinical and molecular genetic findings suggest that GABRE is a likely candidate gene for epilepsy. Nevertheless, functional studies are necessary to better understand pathogenicity of the GABRE-mutations and their associations with epileptic phenotypes.
Identifiants
pubmed: 32588540
doi: 10.1002/mgg3.1388
pmc: PMC7507344
doi:
Substances chimiques
Codon, Initiator
0
Codon, Nonsense
0
GABRE protein, human
0
Receptors, GABA-A
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1388Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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