The C422F mutation of the growth hormone receptor gene is not responsible for short stature

A missense mutation, C422F, was identified in the intracellular domain of G H receptor (GHR) in a Japanese short boy. Although this mutation was previo usly reported in a patient with GH insensitivity syndrome (GHIS), it has no t been clear whether this mutation causes GH insensitivity. To clarify the effect of this mutation on GH signal transduction, mutant GHR was expressed in CHO cells, and its functional properties mere investigated. There were no significant differences in GH-induced tyrosine phosphorylation of STAT5b (signal transducer and activator of transcription) between wild-type GHR ( GHR-wt)- and mutant GHR (GHR-C422F)-expressing cells. Moreover, STAT5-media ted transcriptional activation of GHR-C422F-expressing cells was comparable to that of GHR-wt-expressing cells. These findings indicated that the C422 F mutation of GHR affected neither GH-induced tyrosine phosphorylation nor the transcriptional activation of STAT5. In addition, the analysis of genot ypes and phenotypes of his family revealed that body heights of family memb ers with heterozygous or homozygous C422F mutations were all within normal ranges, with the single exception of the proband. These in vitro and in viv o results indicate that the C422F missense mutation of GHR is a polymorphis m that does not result in GHIS.