The STAT family of proteins are latent cytoplasmic transcription factors. When the proteins are translocated to the nucleus and bind to the corresponding cytokine or growth factor receptor, they are phosphorylated and activated by kinases, interferon, inflammatory factors, epidermal growth factor (EGF) and colony-stimulating factors (CFS) [
1‐
3]. For example, STAT3 is activated by tyrosine phosphorylation in response to EGF and IL-6 [
3]; Stat2 becomes phosphorylated after IFN-α treatment [
4], and IFN-γ induces tyrosine phosphorylation of STAT91 [
5]. The Janus kinase (JAK) family tyrosine phosphorylate STAT family proteins. Activated STAT proteins are translocated to the nucleus to promote transcription, forming the classic JAK-STAT pathway, which is involved in many important biological signal transmissions [
6]. There are many members of the STAT family, 7 of which have been clearly defined: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b and STAT6 [
7,
8]. Among them, STAT1 was the first identified, and it is activated by IFN-α/β [
6,
9], which plays an important role in autoimmune diseases [
10], such as asthma [
11], rheumatoid arthritis [
12], and inflammatory bowel disease [
13]. Mutations in STAT1 can affect the immune function mediated by IFN-γ and IFN-α/β, thereby affecting host immune defence capacity and increasing susceptibility to mycobacteria, fungi and viruses [
14]. STAT1 is both a target of loss-of function (LOF) and GOF mutations [
15]. Since STAT1 GOF mutations were first reported in 2011 [
16], they have been identified in a growing number of patients and have attracted increasing attention.
GOF mutations in STAT1 are frequently enriched in the coiled-coil.
domain or DNA-binding domain [
17], with a variety of clinical manifestations, including CMC infection, autoimmune diseases, and infection leading to early death [
18]. Here, we report a case of pathogenic STAT1 GOF mutation in a young male in China with severe, recurrent and persistent pulmonary bacterial infections and aphthous stomatitis since childhood and who then developed bronchiectasis and increased IgA. The patient has undergone many repeated examinations in the past 10 years to confirm the diagnosis. However, genetic analysis was not performed until at age 17, revealing a novel STAT1 GOF mutation (c.986C> G). We propose that patients with unexplained chronic aphthous stomatitis, pulmonary bacterial infections, bronchiectasis and an increase in immunoglobulin IgA may carry STAT1 GOF mutations.