Key result
More than 90 GHR mutations relevant to human short stature and four GHR defects associated with chicken dwarfism have been described, which interfere with GH-GHR interaction, dimerization, signaling, and expression.
This review summarizes over 90 known GHR mutations that disrupt the GH-GHR-IGF-1 axis and lead to dwarf phenotypes in humans and chickens.
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May aid molecular diagnosis of GH insensitivity; extends mutation spectrum but leaves clinical translation open.
Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, process dysfunctions in the GH⁻GHR⁻IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH⁻GHR⁻IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development.
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Lin et al. (2018) conducted a review in Dwarfism (Laron syndrome, idiopathic short stature). Growth Hormone Receptor (GHR) mutations vs. Normal GHR was evaluated. More than 90 GHR mutations relevant to human short stature and four GHR defects associated with chicken dwarfism have been described, which interfere with GH-GHR interaction, dimerization, signaling, and expression.
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