title: Cryptococcal osteomyelitis in a child with a novel compound mutation of the IL12RB1 gene.
abstract: 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.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. siojr@mahidol.ac.th
authors.forename: Orathai
authors.initials: O
authors.lastname: Jirapongsananuruk
authors.forename: Voravich
authors.initials: V
authors.lastname: Luangwedchakarn
authors.forename: Julie E
authors.initials: JE
authors.lastname: Niemela
authors.forename: Punchama
authors.initials: P
authors.lastname: Pacharn
authors.forename: Nualanong
authors.initials: N
authors.lastname: Visitsunthorn
authors.forename: Charin
authors.initials: C
authors.lastname: Thepthai
authors.forename: Pakit
authors.initials: P
authors.lastname: Vichyanond
authors.forename: Surapon
authors.initials: S
authors.lastname: Piboonpocanun
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
mesh_terms: D002469:Cell Separation; D002675:Child, Preschool; D003453:Cryptococcosis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009154:Mutation; D009164:Mycobacterium Infections / Q000150:complications / Q000235:genetics; D010019:Osteomyelitis / Q000235:genetics* / Q000382:microbiology; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D012480:Salmonella Infections / Q000150:complications / Q000235:genetics; D018805:Sepsis / Q000150:complications / Q000235:genetics
chemical_list: C508438:IL12RB1 protein, human; D053707:Receptors, Interleukin-12