التفاصيل البيبلوغرافية
| العنوان: |
Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19 |
| المؤلفون: |
Xavier Solanich, Gardenia Vargas-Parra, Caspar I. van der Made, Annet Simons, Janneke Schuurs-Hoeijmakers, Arnau Antolí, Jesús del Valle, Gemma Rocamora-Blanch, Fernando Setién, Manel Esteller, Simon V. van Reijmersdal, Antoni Riera-Mestre, Joan Sabater-Riera, Gabriel Capellá, Frank L. van de Veerdonk, Ben van der Hoven, Xavier Corbella, Alexander Hoischen, Conxi Lázaro |
| المصدر: |
Frontiers in Immunology, Vol 12 (2021) |
| بيانات النشر: |
Frontiers Media S.A., 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Immunologic diseases. Allergy |
| مصطلحات موضوعية: |
COVID-19, SARS-CoV-2, host genetics, TLR7, immunodeficiency, genetic screening, Immunologic diseases. Allergy, RC581-607 |
| الوصف: |
IntroductionLoss-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.MethodsWe 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.ResultsTLR7 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.ConclusionsThis 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. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.719115/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2021.719115 |
| URL الوصول: |
https://doaj.org/article/a40c83c79e0d437386a867c3022a1699 |
| رقم الانضمام: |
edsdoj.40c83c79e0d437386a867c3022a1699 |
| قاعدة البيانات: |
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