The etiology of growth failure is unknown for many children with marked short stature. Recent studies have shown heterozygous GH receptor gene mutations in some children with marked short stature not due to classic GH deficiency (idiopathic short stature or ISS) who were selected for study because of low GHBP levels (NEJM 333:1093, 1995). To assess whether partial GH insensitivity due to heterozygous GH receptor gene mutations exists in a less selective population with ISS, we have analyzed the GH receptor genes in 48 out of 121 ISS children enrolled in a long-term clinical trial of GH therapy. These patients have been treated for up to nine years with GH (0.3 mg/kg/wk). Analyses of DNA for mutations in the GH receptor gene were performed using single-strand conformation polymorphism analysis and DNA sequencing. Approximately 10% of the ISS patients tested had heterozygous GH receptor gene mutations. These mutations affected both the extracellular portion and intracellular portion of the GH receptor gene. None of a normal stature control group (0/34) was found to have heterozygous gene mutations. Our findings support the concept that partial GH insensitivity associated with heterozygous GH receptor gene mutations is a significant cause of growth failure. These patients are only partially resistant, and do respond to treatment with GH, albeit at higher doses. The diagnosis of partial GH insensitivity due to heterozygous GH receptor gene mutations should be considered in patients with severe growth failure not due to classic GH deficiency.
|Original language||English (US)|
|Number of pages||2|
|Journal||Endocrinology and Metabolism, Supplement|
|State||Published - Jan 1 1997|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism