dc.contributor.author | Rice, Gillian I. | |
dc.contributor.author | Park, Sehoon | |
dc.contributor.author | Gavazzi, Francesco | |
dc.contributor.author | Adang, Laura A. | |
dc.contributor.author | Ayuk, Loveline A. | |
dc.contributor.author | Van Eyck, Lien | |
dc.contributor.author | Seabra, Luis | |
dc.contributor.author | Barrea, Christophe | |
dc.contributor.author | Battini, Roberta | |
dc.contributor.author | Belot, Alexandre | |
dc.contributor.author | Berg, Stefan | |
dc.contributor.author | Billette de Villemeur, Thierry | |
dc.contributor.author | Bley, Annette E. | |
dc.contributor.author | Blumkin, Lubov | |
dc.contributor.author | Boespflug‐Tanguy, Odile | |
dc.contributor.author | Briggs, Tracy A. | |
dc.contributor.author | Brimble, Elise | |
dc.contributor.author | Dale, Russell C. | |
dc.contributor.author | Darin, Niklas | |
dc.contributor.author | Debray, François Guillaume | |
dc.contributor.author | De Giorgis, Valentina | |
dc.contributor.author | Denecke, Jonas | |
dc.contributor.author | Doummar, Diane | |
dc.contributor.author | Drake af Hagelsrum, Gunilla | |
dc.contributor.author | Eleftheriou, Despina | |
dc.contributor.author | Estienne, Margherita | |
dc.contributor.author | Fazzi, Elisa | |
dc.contributor.author | Feillet, François | |
dc.contributor.author | Galli, Jessica | |
dc.contributor.author | Hartog, Nicholas | |
dc.contributor.author | Harvengt, Julie | |
dc.contributor.author | Heron, Bénédicte | |
dc.contributor.author | Heron, Delphine | |
dc.contributor.author | Kelly, Diedre A. | |
dc.contributor.author | Lev, Dorit | |
dc.contributor.author | Levrat, Virginie | |
dc.contributor.author | Livingston, John H. | |
dc.contributor.author | Martí Carrera, María Itxaso | |
dc.contributor.author | Mignot, Cyril | |
dc.contributor.author | Mochel, Fanny | |
dc.contributor.author | Nougues, Marie Christine | |
dc.contributor.author | Oppermann, Ilena | |
dc.contributor.author | Pérez Dueñas, Belén | |
dc.contributor.author | Popp, Bernt | |
dc.contributor.author | Rodero, Mathieu P. | |
dc.contributor.author | Rodríguez, Diana | |
dc.contributor.author | Saletti, Veronica | |
dc.contributor.author | Sharpe, Cia | |
dc.contributor.author | Tonduti, Davide | |
dc.contributor.author | Vadlamani, Gayatri | |
dc.contributor.author | Van Haren, Keith | |
dc.contributor.author | Tomás Vila, Miguel | |
dc.contributor.author | Vogt, Julie | |
dc.contributor.author | Wassmer, Evangeline | |
dc.contributor.author | Wiedemann, Arnaud | |
dc.contributor.author | Wilson, Callum J. | |
dc.contributor.author | Zerem, Ayelet | |
dc.contributor.author | Zweier, Christiane | |
dc.contributor.author | Zuberi, Sameer M. | |
dc.contributor.author | Orcesi, Simona | |
dc.contributor.author | Vanderver, Adeline L. | |
dc.contributor.author | Hur, Sun | |
dc.contributor.author | Crow, Yanick J. | |
dc.date.accessioned | 2020-04-14T20:10:52Z | |
dc.date.available | 2020-04-14T20:10:52Z | |
dc.date.issued | 2020-01 | |
dc.identifier.citation | Human Mutation 41(4) : 837-849 (2019) | es_ES |
dc.identifier.issn | 1059-7794 | |
dc.identifier.issn | 1098-1004 | |
dc.identifier.uri | http://hdl.handle.net/10810/42692 | |
dc.description.abstract | IFIH1 gain-of-function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi-Goutieres syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate. | es_ES |
dc.description.sponsorship | Yanick J. Crow acknowledges The University of Maryland Brain and Tissue Bank of the NIH NeuroBioBank. Yanick J. Crow acknowledges the European Research Council (786142-E-T1IFNs), a state subsidy managed by the National Research Agency (France) under the "Investments for the Future" program bearing the reference ANR-10-IAHU-01 and the MSDAvenir fund (DEVO-DECODE Project). Tracy A. Briggs acknowledges the National Institute for Health Research (NIHR; NIHR Transitional Research Fellowship, TRF-2016-09-002; with the views expressed were those of the author and not necessarily those of the NHS, the NIHR or the Department of Health). Adeline L. Vanderver is supported by the Kamens endowed chair for Translational Neurotherapeutics and the Myelin Disorders Bioregistry Project. Adeline L. Vanderver and Laura A. Adang acknowledge the CURE Pennsylvania Frontiers in Leukodystrophy grant and U01HD082806. Laura A. Adang also acknowledges the National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR001879. Lien Van Eyck received funding from Research Foundation Flanders (FWO). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/786142 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Aicardi-Goutieres syndrome | es_ES |
dc.subject | IFIH1 | es_ES |
dc.subject | MDA5 | es_ES |
dc.subject | Singleton Merten syndrome | es_ES |
dc.subject | type I interferonopathy | es_ES |
dc.subject | function mutation | es_ES |
dc.subject | disease | es_ES |
dc.title | Genetic and phenotypic spectrum associated with IFIH1 gain‐of‐function | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://onlinelibrary.wiley.com/doi/full/10.1002/humu.23975 | es_ES |
dc.identifier.doi | 10.1002/humu.23975 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Pediatría | |
dc.departamentoeu | Pediatria | |