Defects in growth hormone receptor signaling.
Severe growth failure and insulin-like growth factor (IGF) deficiency were first reported 40 years ago in patients who ultimately proved to have mutations in the gene encoding the growth hormone receptor (GHR). So far, over 250 similar patients, encompassing more than 60 different mutations of GHR, have been reported. The GHR is a member of the cytokine receptor superfamily and has been shown to signal, at least in part, through the Janus-family tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Six patients, from five distinct families, have been reported to have phenotypes similar to that of patients with GHR defects but with wild-type receptors and homozygosity for five different mutations of the STAT5b gene. These patients define a new cause of GH insensitivity and primary IGF deficiency and confirm the crucial role of STAT5b in GH-mediated IGF-I gene transcription.
Rosenfeld
Ron G
RG
Lucile Packard Foundation for Children's Health, 400 Hamilton Avenue, Suite 340, Palo Alto, CA 94201, USA. ron.rosenfeld@lpfch.org
Belgorosky
Alicia
A
Camacho-Hubner
Cecelia
C
Savage
M O
MO
Wit
J M
JM
Hwa
Vivian
V
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D005260:Female; D006130:Growth Disorders / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D009154:Mutation; D011986:Receptors, Somatotropin / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D053612:Janus Kinases