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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorSalpietro, Vincenzo
dc.contributor.authorDixon, Christine L
dc.contributor.authorGuo, Hui
dc.contributor.authorBello, Oscar D
dc.contributor.authorVandrovcova, Jana
dc.contributor.authorEfthymiou, Stephanie
dc.contributor.authorRaspall Chaure, Miquel
dc.contributor.authorMacaya Ruíz, Alfons
dc.date.accessioned2019-08-09T06:48:01Z
dc.date.available2019-08-09T06:48:01Z
dc.date.issued2019-07-12
dc.identifier.citationSalpietro V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, et al. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders. Nat Commun. 2019;10(1):3094.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11351/4256
dc.descriptionNeurodevelopmental disorders; AMPA; GluA2
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.
dc.language.isoeng
dc.publisherNature Research
dc.relation.ispartofseriesNature Communications;10(1)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectTrastorns del desenvolupament - Aspectes genètics
dc.subjectProteïnes de membrana
dc.subjectMutació (Biologia)
dc.subject.meshNeurodevelopmental Disorders
dc.subject.mesh/genetics
dc.subject.meshReceptors, AMPA
dc.subject.meshMutation
dc.titleAMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41467-019-10910-w
dc.subject.decstrastornos del desarrollo neurológico
dc.subject.decs/genética
dc.subject.decsreceptores AMPA
dc.subject.decsmutación
dc.relation.publishversionhttps://www.nature.com/articles/s41467-019-10910-w
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Salpietro V] Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK. Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto "Giannina Gaslini", Genoa, Italy. Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy. [Dixon CL, Bello OD] Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK. [Guo H] Department of Genome Sciences, University of Washington School of Medicine, Seattle, USA. Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China. [Vandrovcova J] Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK. [Efthymiou S] Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London, UK. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK. [Raspall-Chaure M, Macaya A] Servei de Neurologia Pediatrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain.
dc.identifier.pmid31300657
dc.identifier.wosWOS:000475295700001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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