dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Salpietro, Vincenzo |
dc.contributor.author | Dixon, Christine L |
dc.contributor.author | Guo, Hui |
dc.contributor.author | Bello, Oscar D |
dc.contributor.author | Vandrovcova, Jana |
dc.contributor.author | Efthymiou, Stephanie |
dc.contributor.author | Raspall Chaure, Miquel |
dc.contributor.author | Macaya Ruíz, Alfons |
dc.date.accessioned | 2019-08-09T06:48:01Z |
dc.date.available | 2019-08-09T06:48:01Z |
dc.date.issued | 2019-07-12 |
dc.identifier.citation | Salpietro 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.issn | 2041-1723 |
dc.identifier.uri | https://hdl.handle.net/11351/4256 |
dc.description | Neurodevelopmental disorders; AMPA; GluA2 |
dc.description.abstract | AMPA 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.iso | eng |
dc.publisher | Nature Research |
dc.relation.ispartofseries | Nature Communications;10(1) |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Trastorns del desenvolupament - Aspectes genètics |
dc.subject | Proteïnes de membrana |
dc.subject | Mutació (Biologia) |
dc.subject.mesh | Neurodevelopmental Disorders |
dc.subject.mesh | /genetics |
dc.subject.mesh | Receptors, AMPA |
dc.subject.mesh | Mutation |
dc.title | AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1038/s41467-019-10910-w |
dc.subject.decs | trastornos del desarrollo neurológico |
dc.subject.decs | /genética |
dc.subject.decs | receptores AMPA |
dc.subject.decs | mutación |
dc.relation.publishversion | https://www.nature.com/articles/s41467-019-10910-w |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 31300657 |
dc.identifier.wos | WOS:000475295700001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |