Identification of a growth hormone mutation responsible for short stature

A heterozygous single base missense substitution in exon 4, which converted codon 77 from arginine to cysteine, has been identified in a child with severe growth retardation. The mutant GH fails to stimulate GH signal transduction by itself, despite possessing a higher affinity than the wild-type molecule for GHBP, and appears to have a dominant antagonistic effect on the protein phosphorylation activity of wild-type GH.