Heterozygous Missense Mutation in the Coiled-Coil Domain of STAT5B

We describe one patient with a heterozygous missense mutation in the coiled-coil domain of STAT5B. This patient presented with leukocytosis, lymphadenopathy, splenomegaly, necrotizing granulomas, hyper-IgM and autoimmune thrombocytopenia. Mutant STAT5B protein was shown to dominantly-interfere with IL2-induced transcriptional activity resulting in global downregulation of STAT5-regulated genes in patient T cells. The patient exhibited an increase in CD4+ T effector memory cells in the peripheral blood and these cells were resistant to restimulation-induced cell death in vitro. ]]>
Patient samples were chosen for inclusion in the project based on the following criteria: Patient, parents and other family members are available DNA was available for use in whole genome or exome sequencing Informed consent documentation ]]>