Mild Phenotype in Functionally Validated STAT1 Gain-of-Function Disease Due to a Novel DNA-Binding Variant.
Bahri Can Duran, Caner Aytekin, Miyuki Tsumura et al.
✦ AI-curated · Sources linked
Case in brief
A case report describes four patients with STAT1 gain-of-function disease, focusing on three related individuals with a novel p.Leu400Pro variant. These patients exhibited early-onset chronic mucocutaneous candidiasis but maintained a mild clinical course without severe infections or autoimmunity over eight years. In contrast, an unrelated patient with a different variant experienced severe multisystem autoimmunity, which improved with ruxolitinib prior to hematopoietic stem cell transplantation.
What made this case unusual
The novel p.Leu400Pro variant in the DNA-binding domain of STAT1 is associated with a mild phenotype, contrasting with the severe manifestations seen in other variants.
Diagnostic / clinical pearl
Clinicians should consider the specific STAT1 variant when assessing disease severity and potential management strategies in patients with STAT1 gain-of-function disease.
Why it matters
Understanding the mutation-level variability in STAT1-GOF disease can guide personalized treatment approaches and improve patient outcomes.