A Novel Dominant Negative Variant of IRF8 in a Mother and Son: Clinical, Phenotypic and Biological Characteristics

Background: Genetic testing of a child with persistent EBV viremia identified a novel variant c.1279dupT (p.*427Leuext*42) in interferon regulatory factor 8 (IRF8). The same variant was also found in his mother, who shortly thereafter was diagnosed with an HPV+ tumor. The maternal grandparents lacked this variant. Objective: We sought to examine the pathogenicity of the identified IRF8 variant and its phenotypic and functional characteristics in the proband and his mother. Methods: Immune cell enumeration, immunophenotypic and functional flow cytometry, NK cell cytotoxicity, MALDI-TOF mass spectrometry, TCRVb spectratyping, RNA sequencing, OLink proteomics, Sanger sequencing, Immunoblotting, Molecular cloning, Immunofluorescence microscopy and Image analysis were used in this study. Overall design: RNAseq data from 3 human untreated samples: Control (n=1) and IRF8 variant (mother and son; variant c.1279dupT (p.*427Leuext*42), n=2) donors