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dc.contributor.authorRankin, Julia
dc.date.accessioned2019-11-29T15:59:21Z
dc.date.available2019-11-29T15:59:21Z
dc.date.issued2019-07
dc.identifier.citationSalpietro V [et al]. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nature Communications. 2019 10(1) 3094en_US
dc.identifier.pmid31300657
dc.identifier.doi10.1038/s41467-019-10910-w
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621131
dc.description.abstractAMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission.en_US
dc.language.isoenen_US
dc.publisherNatureen_US
dc.relation.urlhttp://dx.doi.org/10.1038/s41467-019-10910-wen_US
dc.rightsThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holderen_US
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen_US
dc.titleAMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disordersen_US
dc.typeJournal Articleen_US
dc.identifier.journalNature Communicationsen_US
dc.identifier.pmcidPMC6626132
dc.description.noteThis article is freely available online via Open Access. Click on the Publisher URL to access the full-text via the publisher's site.en_US
dc.type.versionPublisheden_US


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