Project description:TFRC, also known as CD71, regulates the uptake of transferrin-bound iron into cells through receptor-mediated endocytosis. In a patient with a combined immunodeficiency, we identified a homozygous missense mutation in TFRC gene leading to R22W amino acid change in the cytoplasmic tail of the receptor. This mutation impairs the endocytosis of TFRC, which results in profound aberrations in the immune system.
2024-01-31 | GSE243237 | GEO
Project description:Gene Mutation Causes a Syndrome of Combined Immunodeficiency
| PRJNA690210 | ENA
Project description:A de novo mutation in ITPR3 causes severe combined immunodeficiency
Project description:the same population of EPCs was detected in bladder cancer patients. The EPCs, whose function could be reversed via anti-CD71 treatment, were induced by the circRNA TFRC (circular RNA derived from the transferrin receptor mRNA; cTFRC) in bladder cancer exosomes.
Project description:An IRF4 de novo mutation affecting the DNA binding domain of encoded IRF4 protein (mutDBD) was identified in a patient presenting with combined immunodeficiency. The patient exhibited profound susceptibility to opportunistic infections notably Pneumocystis jirovecii and humoral immunodeficiency caused by a failure of terminal B cell differentiation. A heterozygous IRF4 missense variant resulting in a phenylalanine-to-leucine replacement within the interferon activation domain of the encoded IRF4 protein (mutIAD) was identified in three patients from a multigenerational family suffering from a novel autosomal dominant disease predominantly presenting as a hypogammaglobulinemia with recurrent infections. In this experiment we aimed to investigate the effect of the two different mutations on IRF4 regulated transcription.
Project description:An IRF4 de novo mutation affecting the DNA binding domain of encoded IRF4 protein (mutDBD) was identified in a patient presenting with combined immunodeficiency. The patient exhibited profound susceptibility to opportunistic infections notably Pneumocystis jirovecii and humoral immunodeficiency caused by a failure of terminal B cell differentiation. A heterozygous IRF4 missense variant resulting in a phenylalanine-to-leucine replacement within the interferon activation domain of the encoded IRF4 protein (mutIAD) was identified in three patients from a multigenerational family suffering from a novel autosomal dominant disease predominantly presenting as a hypogammaglobulinemia with recurrent infections. In this experiment we aimed to investigate the effect of the two different mutations on IRF4 genomic binding.
Project description:IKKα is a critical regulator of the non-canonical NF-KB signalling pathway. In patients with combined immunodeficiency, we identified a homozygous missense mutation in CHUK gene, coding for IKKα protein, leading to G167R amino acid change in the kinase domain of the protein. This mutation impairs the kinase activity of IKKα, which results in a range of aberratins in innate and adaptive immunity.
