| Autor: |
Fenja Markus, Chloé Angelini, Aurelien Trimouille, Gabrielle Rudolf, Gaetan Lesca, Cyril Goizet, Eulalie Lasseaux, Benoit Arveiler, Marjon vanSlegtenhorst, Alice S. Brooks, Rami Abou Jamra, Georg‐Christoph Korenke, John Neidhardt, Marta Owczarek‐Lipska |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Molecular Genetics & Genomic Medicine, Vol 8, Iss 9, Pp n/a-n/a (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2324-9269 |
| DOI: |
10.1002/mgg3.1388 |
| Popis: |
Abstract 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 GABAA receptor subunit ε gene (GABRE), including one nonsense (NM_004961.3: c.399C>A, p.Tyr133*), two missense variants (NM_004961.3: c.664G>A, p.Glu222Lys; NM_004961.3: c.1045G>A, p.Val349Ile), and one variant affecting the translation initiation codon (NM_004961.3: c.1A>G, p.Met1?) in four unrelated families. 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. |
| Databáze: |
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