Signal transducer and activator of transcription 3 (STAT3) gain-of-function (GOF)
syndrome is an early-onset monogenic inborn error of immunity characterized by multi-organ
autoimmune disorders, growth failure and lymphoproliferation. We describe that STAT3
GOF syndrome may be presented with hypogammaglobulinemia and recurrent severe upper
and lower respiratory tract infections. In addition, the patient had lymphoproliferation,
short stature and interstitial lung disease. Chest CT examinations showed mild bronchiectasis
with areas of non-fibrosing alveolar-interstitial disease and maldevelopment of bilateral
first ribs. By using Sanger sequencing, we revealed a novel c.508G>C, p.D170H STAT3
variant affecting the coiled coil domain of STAT3. Functional studies confirmed that
p.D170H was a GOF variant as showed by increased pSTAT3 and STAT3 transcriptional
activity. Our observation suggests that STAT3 GOF syndrome can manifest in early childhood
with hypogammaglobulinemia and recurrent severe respiratory tract infections. We suggest
that patients with lymphoproliferation, hypogammaglobulinemia and severe, recurrent
infections should be screened for STAT3 variants even if autoimmune manifestations
are missing.
