Chronic mucocutaneous candidiasis, mycobacterial infections and rosacea in a Mexican adult with STAT1 gain of function

Abstract

STAT1 is a cytoplasmic transcription factor associated with cell growth regulation, differentiation, proliferation, metabolism, and apoptosis. IFN-mediated JAK/STAT signaling pathway is involved in eliminating intracellular pathogens and viruses. However, pathogenic variants in STAT1 can result in impaired or increased function. Increased activity or function in STAT1 was described in 2011 and is characterized by excessive phosphorylation of the transcription factor. Carriers can develop autoimmune and inflammatory diseases and are susceptible to fungal, viral, and bacterial infections. The early and common manifestation is chronic mucocutaneous candidiasis. Here, we report a clinical case of a patient with increased STAT1 activity or gain of function, which started in the first year of his life. He is currently 27 years old and has presented bacillus Calmette-Guérin and Mycobacterium tuberculosis infection, chronic mucocutaneous candidiasis, tinea capitis, and facial and ocular rosacea. HIV infection was ruled out. Given the clinical manifestations, an inborn error of immunity was suspected, specifically STAT1 with gain of function. The diagnosis was corroborated by the sequencing of multiple genes associated with inborn errors of immunity. The pathogenic variant c.961A>G (p.Arg321Gly) in the STAT1 gene, previously reported as a gain of function mutation, was found in the patient. Finally, this case illustrates that mutations in immune-associated genes can contribute to producing severe and recurrent infections, even in adult patients. Chronic mucocutaneous candidiasis should raise suspicion of gain of function in STAT1.