Gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation-related primary immunodeficiency is associated with disseminated mucormycosis

摘要

Signal transducer and activator of transcription 1 (STAT1) belongs to a family of transcription factors that mediate growth factor and cytokine signaling. Complete recessive mutations in STAT1 cause susceptibility to viral, mycobacterial, and bacterial infections and are fatal early in life. In contrast, heterozygous dominant negative mutations in STAT1 cause mild disseminated mycobacterial infections.1 Recently, heterozygous dominant gain-of-function (GOF) mutations in STAT1 were described as causing impaired STAT1 dephosphorylation, diminished IL-17-producing T-cell numbers, and chronic mucocutaneous candidi-asis (CMC). These GOF mutations have also been associated with intracellular dimorphic fungal infections, disseminated coccidioidomycosis, histoplasmosis, and cases of wild-type forkhead box protein 3 (F0XP3) immunodysregulation, polyen-docrinopathy, enteropathy, X-linked (IPEX)-like syndrome.4 Progressive multifocal leukoencephalopathy, autoimmunity, arterial aneurysms, and squamous cell cancers have also been reported.We identified a novel GOF STAT1 mutation in a patient with disseminated mucormycosis caused by Apophysomyces trapeziformis. Previous reports of A trapeziformis infection were associated with penetrating trauma in immunocompetent hosts.6 This is the first description of a primary immunodeficiency linked to disseminated mucormycosis.