Cryptococcal osteomyelitis in a child with a novel compound mutation of the IL12RB1 gene.

The IL-12p40/IL-12Rbeta1 and IFN-gammaR1/IFN-gammaR2/STAT1 signaling pathways are important for clearing intracellular bacteria. Genetic defects within these pathways are associated with increased susceptibility to intracellular pathogens. Among these, IL-12Rbeta1 deficiency is the most common defect and leads to infections with Salmonella and Mycobacterium spp. We report a child who presented with Cryptococcal osteomyelitis and history of disseminated Mycobacterial infection and recurrent Salmonella septicemia. Flow cytometry showed defective expression of IL-12Rbeta1. Mutation analysis revealed a novel compound heterozygous mutation of IL12RB1, c.625C>T, p.Q209X was found in exon 7 on the paternal allele and c.710delC, p.P237HfsX5 was found in exon 8 on the maternal allele. As these mutations each result in a stop codon before the last spliceable exon, the transcripts likely underwent nonsense mediated decay, leading to a lack of IL12Rbeta1 expression on the cell surface and eradicating signaling via the IL12 signaling pathway.