Human growth disorders associated with impaired GH action: Defects in STAT5B and JAK2

Growth hormone (GH) promotes postnatal human growth primarily by regulating insulin-like growth factor (IGF)-I production through activation of the GH receptor (GHR)-JAK2-signal transducer and activator of transcription (STAT)-5B signaling pathway. Inactivating STAT5B mutations, both autosomal recessive (AR) and dominant-negative (DN), are causal of a spectrum of GH insensitivity (GHI) syndrome, IGF-I deficiency and postnatal growth failure. Only AR STAT5B defects, however, confer additional characteristics of immune dysfunction which can manifest as chronic, potentially fatal, pulmonary disease. Somatic activating STAT5B and JAK2 mutations are associated with a plethora of immune abnormalities but appear not to impact human linear growth. In this review, molecular defects associated with STAT5B deficiency is highlighted and insights towards understanding human growth and immunity is emphasized.

Automated summary

Growth hormone promotes human postnatal growth by regulating IGF-I production through the GH receptor-JAK2-STAT5B signaling pathway. Mutations associated with STAT5B deficiency can cause GHI syndrome and immune dysfunction, potentially leading to fatal consequences. Somatic activating STAT5B mutations are linked to immune abnormalities but do not impact human linear growth.