COVID-19 researchGene: TLR7
PMID: 32706371 - van der Made et al 2020 - report 2 unrelated families from the Netherlands (1 family Dutch ancestry, 1 family African ancestry) in which 2 brothers from each family were hospitalized for SARS-CoV-2 infection. All were aged below 35 years. Using whole exome sequencing they identified a 4-nucleotide hemizygous deletion in TLR7 was identified, leading to a predicted total loss of function of TLR7 in the two brothers from family 1. The mother appeared to be a heterozygous carrier. In family 2 a missense variant (NM_016562.3: c.2383G>T; p.[Val795Phe]) in TLR7 was identified in both brothers, that is predicted to be deleterious. In PBMCs isolated from patients, the identified nonsense and missense TLR7 variants impaired mRNA expression of TLR7 on stimulation with the TLR7 agonist imiquimod, showing a loss-of-function effect. The patients also showed an impaired transcriptional host type I IFN response downstream of the TLR7 pathway, as evidenced by impaired upregulation expression of IRF7, IFNB1, and ISG15.
Created: 27 Jul 2020, 10 a.m. | Last Modified: 27 Jul 2020, 10 a.m.
Panel Version: 1.60
Evidence Summary from Illumina curation team: The TLR7 gene encodes for toll -like receptor 7 protein, an endosomal receptor that plays a key role in innate and adaptive immunity. Toll-like receptors are pattern recognition receptors, which control host immune response against pathogens through recognition of molecular signatures. TLR7 recognizes uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analog (reviewed by Freund et al. 2019). Tlr7 deficient mice show an increased susceptibility to West Nile Virus (Town et al. (2009) and recently, Mukherjee et al. (2019) identified TLR7 polymorphisms associated with susceptibility to viral infections in an East Asian population Mukherjee et al. (2019).
Created: 28 May 2020, 3:12 p.m. | Last Modified: 28 May 2020, 3:12 p.m.
Panel Version: 0.347
Identified through an OMIM search for potential viral susceptibility genes, and subsequently triaged/reviewed by Illumina curation team.
Created: 28 May 2020, 12:36 p.m. | Last Modified: 28 May 2020, 12:36 p.m.
Panel Version: 0.336
Publications for gene: TLR7 were set to
Mode of inheritance for gene: TLR7 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females
gene: TLR7 was added gene: TLR7 was added to COVID-19 research. Sources: Expert list,OMIM,Expert Review Green Mode of inheritance for gene: TLR7 was set to Unknown