title: STAT5B deficiency: Impacts on human growth and immunity.
abstract: Growth hormone (GH) promotes postnatal human growth primarily by regulating insulin-like growth factor (IGF)-I production through activation of the GH receptor (GHR)-signal transducer and activator of transcription (STAT)-5B signaling cascade. The critical importance of STAT5B in human IGF-I production was confirmed with the identification of the first homozygous, autosomal recessive, STAT5B mutation in a young female patient who phenotypically resembled patients with classical growth hormone insensitivity (GHI) syndrome (Laron syndrome) due to mutations in the GHR gene, presenting with severe postnatal growth failure and marked IGF-I deficiency. Of note, the closely related STAT5A, which shares >95% amino acid identity with STAT5B, could not compensate for loss of functional STAT5B. To date, 7 homozygous, inactivating, STAT5B mutations in 10 patients have been reported. STAT5B deficient patients, unlike patients deficient in GHR, can also present with a novel, potentially fatal, primary immunodeficiency, which can manifest as chronic pulmonary disease. STAT5B deficiency may be underestimated in endocrine, immunology and pulmonary clinics.
authors.affiliation: Cincinnati Center for Growth Disorders, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229, United States. Electronic address: vivian.hwa@cchmc.org.
authors.forename: Vivian
authors.initials: V
authors.lastname: Hwa
mesh_terms: D000818:Animals; D006130:Growth Disorders / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D046150:Laron Syndrome / Q000235:genetics*; D051379:Mice; D009154:Mutation; D050799:STAT5 Transcription Factor / Q000235:genetics*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D050799:STAT5 Transcription Factor; D007334:Insulin-Like Growth Factor I
keywords: Growth hormone insensitivity; IGF-I deficiency; STAT5B mutations; T regulatory cell deficiency