| http://purl.uniprot.org/citations/35047853 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35047853 | http://www.w3.org/2000/01/rdf-schema#comment | "De novo gain-of-function mutations of SCN8A are a significant cause of developmental and epileptic encephalopathy (DEE) (MIM: 614558). The severely affected individuals exhibit refractory seizures, developmental delay, and cognitive disabilities, often accompanied by impaired movement. Individuals with the identical SCN8A variant often differ in clinical course, suggesting a role for modifier genes in disease severity. In a previous study we demonstrated genetic linkage between a hypomorphic mutation in the Gabra2 gene and seizure severity in a mouse model of the human SCN8A pathogenic variant p.Arg1872Trp. Homozygosity for the hypomorphic Gabra2 mutation was associated with early seizure onset and shortened lifespan. We have now confirmed Gabra2 as the modifier gene using a knock-in allele that corrects the splice site variant in strain C57BL/6J. Correction of the Gabra2 variant restores transcript abundance, increases the age of seizure onset, and extends survival of the Scn8a mutant mice. GABRA2 encodes the α2 subunit of the GABAA receptor that provides inhibitory input to dendrites and the the axon initial segment of excitatory neurons. Quantitative variation in human GABAA receptor expression could contribute to variation in the severity of genetic epilepsies and suggests a potential therapeutic intervention."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.xhgg.2021.100064"xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/author | "Yu W."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/author | "Williams R.W."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/author | "Meisler M.H."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/author | "Mulligan M.K."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/date | "2022"xsd:gYear |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/name | "HGG Adv"xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/pages | "100064"xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/title | "Correction of the hypomorphic Gabra2 splice site variant in mouse strain C57BL/6J modifies the severity of Scn8a encephalopathy."xsd:string |
| http://purl.uniprot.org/citations/35047853 | http://purl.uniprot.org/core/volume | "3"xsd:string |
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