1. Atypical STAT5B deficiency, severe short stature and mild immunodeficiency associated with a novel homozygous STAT5B Variant
- Author
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Gonul Catli, Wen Gao, Corinne Foley, Berk Özyilmaz, Neslihan Edeer, Gulden Diniz, Monique Losekoot, Jaap van Doorn, Andrew Dauber, Bumin N. Dundar, Jan M. Wit, Vivian Hwa, İstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Gönül Çatlı / 0000-0002-0488-6377, Çatlı, Gönül, Gönül Çatlı / EOU-3210-2022, and Gönül Çatlı / 35783928000
- Subjects
lung disease ,dwarfism ,frameshift mutation ,somatomedin binding protein ,Immune deficiency ,growth hormone insensitivity ,Biochemistry ,somatomedin ,Endocrinology ,genetic variability ,STAT5 Transcription Factor ,genetics ,Insulin-Like Growth Factor I ,bone age ,clinical article ,delayed puberty ,unclassified drug ,prolactin blood level ,STAT5b protein ,female ,human growth hormone ,disease severity ,eczema ,hormone resistance ,prolactin ,insulin growth factor II ,STAT5B deficiency ,STAT5 protein ,protein deficiency ,Article ,amenorrhea ,loss of function mutation ,case report ,Humans ,human ,Molecular Biology ,protein expression ,STAT5B gene ,B lymphocyte ,disease association ,Immunologic Deficiency Syndromes ,insulin growth factor I ,somatomedin C ,short stature ,STAT5B ,STAT5B protein, human ,adolescent ,Growth Hormone ,homozygosity ,acid labile subunit protein ,hypergammaglobulinemia ,metabolism - Abstract
STAT5B 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. © 2022 Elsevier B.V., National Institute of Child Health and Human Development, NICHD: R21 HD098417, This work was supported by the National Institute of Child health and Human Development, R21 HD098417 (to VH).
- Published
- 2023