Clinically, the<unk> -associated phenotype is very diverse. It is characterized by prominent lymphoproliferation, including lymphadenopathy and/or hepatosplenomegaly, as well as early-onset multisystem autoimmunity. Hematologic autoimmunity is most prevalent including autoimmune hemolytic anemia, neutropenia, and/or thrombocytopenia. Others exhibited arthritis, lung disease consistent with lymphocytic interstitial pneumonia, hepatitis, atopic dermatitis, alopecia, and/or scleroderma. Several patients also have recurrent, severe infections and fungal infections with hypogammaglobulinemia. Postnatal short<unk> re, with some exhibiting profound growth failure, is commonly seen. Early-onset type 1 diabetes was also noted in several of these patients. The stereotyped clinical phenotype of<unk>  patients differs distinctly from that associated with germline<unk>  mutations shown to confer a loss-of-function (LOF).<unk>  loss-of-function mutations are responsible for hyperimmunoglobulin E syndrome, also called Job's syndrome, which is characterized by recurrent infections, unusual eczema-like skin rashes, and susceptibility to severe lung infections. While both LOF and<unk>  of<unk>  result in immune deficiency,<unk>  exhibit infections quite distinct from those observed with LOF, along with far more common connective tissue abnormalities. Furthermore, somatic gain-of-function<unk>  mutations are reported in association with solid and hematologic cancers. Therefore, one would have expected that germline<unk>  mutations would have a similar increase the risk of cancer. However, only 1 patient presented with large granular lymphocytic leukemia and 1 parent with Hodgkin lymphoma. The germline and somatic gain-of-function<unk>  mutations appear to result in distinctly different phenotypes.
STAT3 GOF
HL23V
Philadelphia chromosome
Tbx18 transduction
T790M
ABL 
Fusion gene
GcMAF