STAT5b deficiency: Lessons from STAT5b gene mutations

Vivian Hwa, Kari Nadeau, Jan M. Wit, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Growth hormone (GH) regulates insulin-like growth factor (IGF)-I production primarily through activation of the GH receptor (GHR)-signal transducer and activator of transcription (STAT)-5b signaling cascade. One of four STAT proteins (STAT1, -3, -5a and -5b) activated by the GH-GHR system, the critical importance of STAT5b in IGF-I production became evident with the identification of homozygous, autosomal recessive STAT5b mutations in patients who presented with severe postnatal growth failure, growth hormone insensitivity syndrome (GHIS) and marked IGF-I deficiency. Unlike GHIS due to GHR mutations, patients carrying STAT5b mutations also presented with chronic pulmonary disease and evidence of perturbations of T-cell homeostasis. At present, no single treatment(s) is available to improve both poor statural growth and immune deficiency. Continued clinical evaluations of patients with STAT5b mutations and elucidating the impact of the mutation on STAT5b structure and function, are important to understanding the pathophysiology of this rare, complex, disease (MIM 245590).

Original languageEnglish (US)
Pages (from-to)61-75
Number of pages15
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Volume25
Issue number1
DOIs
StatePublished - Feb 2011

Fingerprint

Laron Syndrome
Mutation
Somatotropin Receptors
Genes
Insulin-Like Growth Factor I
STAT Transcription Factors
STAT5 Transcription Factor
Growth
Rare Diseases
Lung Diseases
Growth Hormone
Homeostasis
Chronic Disease
T-Lymphocytes
Therapeutics

Keywords

  • growth hormone insensitivity
  • insulin-like growth factor deficiency
  • signal transducers and activators of transcription 5b
  • STAT5b gene mutations
  • T regulatory cell deficiency

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

STAT5b deficiency : Lessons from STAT5b gene mutations. / Hwa, Vivian; Nadeau, Kari; Wit, Jan M.; Rosenfeld, Ronald (Ron).

In: Best Practice and Research: Clinical Endocrinology and Metabolism, Vol. 25, No. 1, 02.2011, p. 61-75.

Research output: Contribution to journalArticle

Hwa, Vivian ; Nadeau, Kari ; Wit, Jan M. ; Rosenfeld, Ronald (Ron). / STAT5b deficiency : Lessons from STAT5b gene mutations. In: Best Practice and Research: Clinical Endocrinology and Metabolism. 2011 ; Vol. 25, No. 1. pp. 61-75.
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