Novel PI3Kγ Mutation in a 44-Year-Old Man with Chronic Infections and Chronic Pelvic Pain

Abstract

A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…Three candidate SNPs have been replicated in separate publications: TNF, [619][620][621][622][623] IL1A, 619,624 and AOAH. 613,618 TNF and IL1A are important proinflammatory cytokines, and AAOH inactivates lipopolysaccharides.…”

Function, Regulation and Biological Roles of PI3Kγ Variants

“…These data should be interpreted with care, as mutation of five consecutive amino acids in the RBD could affect Gβγ-dependent stimulation of p110γ independently of Ras. Recently, a missense mutation was identified in the Ras-binding domain of p110γ (Val282Ala) in a patient suffering from chronic infections and pelvic pain, which may point to a clinical relevance of Ras p110γ interaction [76].…”