Mycobacterial infections and recurrent osteomyelitis in a patient with an autosomal dominant mutation in IFN-gamma receptor 1 with overexpression of the receptor.
Pamela Rivero-García, Luis Martínez-Robles, Yolanda González et al.
✦ AI-curated · Sources linked
Case in brief
A Mexican man developed severe BCGitis in early childhood, followed by recurrent disseminated mycobacterial infections and vertebral osteomyelitis involving several species. Functional testing showed impaired IFN-γ signaling, including reduced IL-12p40 production after BCG plus IFN-γ stimulation and impaired STAT-1 phosphorylation, alongside increased cell-surface IFN-γR1. Sequencing identified a de novo heterozygous truncating IFNGR1 variant, c.805delT (p.Tyr269Ilefs*8). The variant was associated with accumulation of defective receptor and a dominant-negative effect. He responded to prolonged antimycobacterial therapy.
What made this case unusual
The recurrent vertebral osteomyelitis occurred alongside infections from multiple mycobacterial species and was associated with a de novo IFNGR1 variant that increased cell-surface receptor expression despite impairing IFN-γ signaling.
Diagnostic / clinical pearl
Recurrent infectious osteomyelitis with repeated or disseminated mycobacterial disease should prompt consideration of an underlying defect in IFN-γ signaling, including autosomal dominant IFNGR1 variants.