NLRC4 mutation causes rare autoinflammatory disease.This article discusses research on the role of NLRC4 gene mutations in autoinflammatory syndrome. It references the studies "An Activating NLRC4 Inflammasone Mutation Causes Autoinflammation With Recurrent Macrophage Activation Syndrome" and "Mutation of...
[11] Liang J, Alfano DN, Squires JE, et al. Novel NLRC4 mutation causes a syndrome of perinatal autoinflammation with hemophagocytic lymphohistiocytosis, hepatosplenomegaly, fetal thrombotic vasculopathy, and congenital anemia ...
Methods:We performed whole-exome/genome sequencing and digital droplet PCR (ddPCR) to identify the pathogenic somatic mutation. We used single-cell RNA sequencing (scRNA-seq), intracellular cytokine staining, quantitative PCR, immunohistochemistry and western blotting to define inflammatory signatures and...
27,28. Experiments with FlaTox demonstrated that NAIP/NLRC4 activation in vivo can cause pathology in the absence of ‘priming’ or inflammasome-induced IL-1β/-1818. However, FlaTox has acute lethal effects that make it difficult to model the chronic effects of inappropriate NLRC4 activation...
(syndrome of enterocolitis and auto-inflammation associated with mutation in NLRC4)23,24. Current treatments for NLRC4-MAS/SCAN4 focus on blocking IL-1, however, some patients respond poorly to IL-1 blockade suggesting that targeting upstream mechanisms of cell death may be a more effective ...
The single-stranded DNA (ssDNA) sequence to introduce the C284A mutation was 5′ GATGAACACTTTGAAGTGCCCAAGCTTGAAAGACAAGCCCAAGGTGATCATTATTCAGGCCGCCCG TGGAGGTAAGTGCTGATTGTTTAAAATAACAGGGCATTCCCATTGAGACTTTATCATTTATAGATAGAGAGTACTCTT 3′. A silent HaeIII restriction site was created to genotype the...
With similar findings to Canna et al., Kazmierczak notes, “We showed that the NLRC4 mutation caused the patient's macrophages to produce IL-1β and IL-18 in the absence of infection, and we observed spontaneous formation of the macromolecular inflammasome complex. This abnormal behavior in th...
Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation Letter Nature Genetics 14 September 2014 An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome Letter Nature Genetics 14 September 2014 Access this article Log in via an...
We show that the disease is caused by a de novo gain-of-function mutation in NLRC4 encoding a p.Val341Ala substitution in the HD1 domain of the protein that cosegregates with disease. Mutant NLRC4 causes constitutive IL1FC production and macrophage cell death. Infected macrophages from ...
In summary, we identified the first patient with a novel de novo heterozygous NLRC4 gene mutation contributing to autoinflammatory disease in Malaysia. Our findings reinforce the likely pathogenicity of specific LRR domain mutations in NLRC4 and expand the clinical spectrum of NLRC4 mutations....