Çatlı, GönülGao, WenFoley, CorinneÖzyılmaz, BerkEdeer, NeslihanDiniz, GüldenLosekoot, Moniquevan Doorn, JaapDauber, AndrewDündar, Bumin N.Wit, Jan M.Hwa, Vivian2022-11-082022-11-082022Catli, G., Gao, W., Foley, C., Özyilmaz, B., Edeer, N., Diniz, G., . . . Hwa, V. (2023). Atypical STAT5B deficiency, severe short stature and mild immunodeficiency associated with a novel homozygous STAT5B variant. Molecular and Cellular Endocrinology, 559 doi:10.1016/j.mce.2022.111799https://doi.org/10.1016/j.mce.2022.111799https://hdl.handle.net/20.500.12713/3266STAT5B deficiency, a rare autosomal recessive disorder characterized by severe growth hormone insensitivity (GHI) and immunodeficiency, can manifest as fatal pulmonary complications. We describe atypical STAT5B deficiency associated with a novel homozygous frame-shift STAT5B variant [c.1453delG, p.(Asp485Thrfs*29)] identified in a young 17.6 yr old female subject who had severe postnatal growth impairment, biochemistries typical of GHI, an immune profile notable for hypergammaglobulinaemia and elevated B lymphocytes, and lack of pulmonary disease. Marked elevation of serum prolactin and pathologically diagnosed eczema were evident. In reconstitution studies, the STAT5B p.(Asp485Thrfs*29) was expressed although expression was reduced compared to wild-type STAT5B and a previously identified STAT5B p.(Gln368Profs*9) variant. Both truncated STAT5B peptides could not be activated by GH, nor mobilize to the nucleus. We conclude that an intact, functional, STAT5B is essential for normal GH-mediated growth, while expressed loss-of-function STAT5B variants may alleviate severe immune and pulmonary issues normally associated with STAT5B deficiency.eninfo:eu-repo/semantics/closedAccessGrowth Hormone InsensitivityImmune DeficiencySTAT5BArticle559WOS:0009001072000042-s2.0-85140240403Q210.1016/j.mce.2022.111799N/A