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http://hdl.handle.net/2445/183474
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DC Field | Value | Language |
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dc.contributor.author | Santos Gómez, Ana | - |
dc.contributor.author | Miguez Cabello, Federico | - |
dc.contributor.author | Juliá Palacios, Natalia | - |
dc.contributor.author | García Navas, Deyanira | - |
dc.contributor.author | Soto Insuga, Víctor | - |
dc.contributor.author | García Peñas, Juan J. | - |
dc.contributor.author | Fuentes, Patricia | - |
dc.contributor.author | Ibáñez Micó, Salvador | - |
dc.contributor.author | Cuesta, Laura | - |
dc.contributor.author | Cancho, Ramón | - |
dc.contributor.author | Andreo Lillo, Patricia | - |
dc.contributor.author | Gutiérrez Aguilar, Gema | - |
dc.contributor.author | Alonso Luengo, Olga | - |
dc.contributor.author | Málaga, Ignacio | - |
dc.contributor.author | Hedrera Fernández, Antonio | - |
dc.contributor.author | García Cazorla, Àngels | - |
dc.contributor.author | Soto del Cerro, David | - |
dc.contributor.author | Olivella, Mireia | - |
dc.contributor.author | Altafaj, Xavier | - |
dc.date.accessioned | 2022-02-23T17:58:32Z | - |
dc.date.available | 2022-02-23T17:58:32Z | - |
dc.date.issued | 2021-11-23 | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/2445/183474 | - |
dc.description.abstract | Background: GRIN-related disorders (GRD), the so-called grinpathies, is a group of rare encephalopathies caused by mutations affecting GRIN genes (mostly GRIN1, GRIN2A and GRIN2B genes), which encode for the GluN subunit of the N-methyl D-aspartate (NMDA) type ionotropic glutamate receptors. A growing number of functional studies indicate that GRIN-encoded GluN1 subunit disturbances can be dichotomically classified into gain- and loss-of-function, although intermediate complex scenarios are often present. Methods: In this study, we aimed to delineate the structural and functional alterations of GRIN1 disease-associated variants, and their correlations with clinical symptoms in a Spanish cohort of 15 paediatric encephalopathy patients harbouring these variants. Results: Patients harbouring GRIN1 disease-associated variants have been clinically deeplyphenotyped. Further, using computational and in vitro approaches, we identified different critical checkpoints affecting GluN1 biogenesis (protein stability, subunit assembly and surface trafficking) and/or NMDAR biophysical properties, and their association with GRD clinical symptoms. Conclusions: Our findings show a strong correlation between GRIN1 variants-associated structural and functional outcomes. This structural-functional stratification provides relevant insights of genotypephenotype association, contributing to future precision medicine of GRIN1-related encephalop | - |
dc.format.extent | 19 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | MDPI | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/ijms222312656 | - |
dc.relation.ispartof | International Journal of Molecular Sciences, 2021, vol. 22, num. 23, p. 12656 | - |
dc.relation.uri | https://doi.org/10.3390/ijms222312656 | - |
dc.rights | cc-by (c) Santos Gómez, Ana et al., 2021 | - |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Biomedicina) | - |
dc.subject.classification | Neurotransmissió | - |
dc.subject.classification | Neurobiologia del desenvolupament | - |
dc.subject.other | Neural transmission | - |
dc.subject.other | Developmental neurobiology | - |
dc.title | Paradigmatic de novo GRIN1 variants recapitulate pathophysiological mechanisms underlying GRIN1-related disorder clinical spectrum | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 718020 | - |
dc.date.updated | 2022-02-23T17:58:33Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Institut de Neurociències (UBNeuro)) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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718020.pdf | 4.8 MB | Adobe PDF | View/Open |
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