Chronic mucocutaneous candidiasis due to a rare STAT1 transactivation domain variant

Chronic mucocutaneous candidiasis (CMC) is a clinical phenotype resulting from several distinct inborn errors of immunity that is commonly caused by STAT1 gain-of-function (GOF) mutations. Variants within the transactivation domain (TAD) are rare, representing a small minority of STAT1-GOF cases. We report a 2-year-old girl with refractory onychomycosis and oral and cutaneous candidiasis, carrying a heterozygous STAT1 TAD variant, p.(Thr720Ile). This variant has been reported previously in an adult with CMC and functionally characterized, with increased phosphorylated STAT1 following stimulation and reduced circulating Th17 cells. However, the precise biochemical mechanism by which TAD variants produce this remains less well-defined. This report highlights a rare TAD variant of CMC that initially presented with features resembling inverse psoriasis, emphasizing the role of early genetic diagnosis in coordinating long-term surveillance for malignant, autoimmune, and vascular comorbidities.