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

The IL-12p40/IL-12Rβ1 and IFN-γR1/IFN-
γR2/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-12Rβ1 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-12Rβ1.
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
IL12Rβ1 expression on the cell surface and eradicating signaling via the IL12

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