Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/179929
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Solanich, Xavier | - |
dc.contributor.author | Vargas Parra, Gardenía María | - |
dc.contributor.author | Van Der Made, Caspar I. | - |
dc.contributor.author | Simons, Annet | - |
dc.contributor.author | Schuurs Hoeijmakers, Janneke | - |
dc.contributor.author | Antolí, Arnau | - |
dc.contributor.author | Valle, Jesús del | - |
dc.contributor.author | Rocamora Blanch, Gemma | - |
dc.contributor.author | Setién, Fernando | - |
dc.contributor.author | Esteller, Manel | - |
dc.contributor.author | Van Reijmersdal, Simon V. | - |
dc.contributor.author | Riera Mestre, Antoni | - |
dc.contributor.author | Sabater Riera, Joan | - |
dc.contributor.author | Capellá, G. (Gabriel) | - |
dc.contributor.author | Van De Veerdonk, Frank L. | - |
dc.contributor.author | Van Der Hoven, Ben | - |
dc.contributor.author | Corbella, Xavier | - |
dc.contributor.author | Hoischen, Alexander | - |
dc.contributor.author | Lázaro García, Conxi | - |
dc.date.accessioned | 2021-09-10T09:35:00Z | - |
dc.date.available | 2021-09-10T09:35:00Z | - |
dc.date.issued | 2021-07-23 | - |
dc.identifier.uri | http://hdl.handle.net/2445/179929 | - |
dc.description.abstract | Introduction: Loss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19. Methods: We prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants. Results: TLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect. Conclusions: This study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions. | - |
dc.format.extent | 10 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media SA | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fimmu.2021.719115 | - |
dc.relation.ispartof | Frontiers in Immunology, 2021, vol. 12, num. 719115 | - |
dc.relation.uri | https://doi.org/10.3389/fimmu.2021.719115 | - |
dc.rights | cc by (c) Solanich, Xavier et al., 2021 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | COVID-19 | - |
dc.subject.classification | SARS-CoV-2 | - |
dc.subject.classification | Cribatge genètic | - |
dc.subject.classification | Immunodeficiència | - |
dc.subject.other | COVID-19 | - |
dc.subject.other | SARS-CoV-2 | - |
dc.subject.other | Genetic screening | - |
dc.subject.other | Immunodeficiency | - |
dc.title | Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 716120 | - |
dc.date.updated | 2021-09-10T06:36:13Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 34367187 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Clíniques) Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
fimmu-12-719115.pdf | 859.96 kB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License