GHSR mutations and delayed puberty

Constitutional delay of growth and puberty (CDGP) is among the most commonly diagnosed growth disorders and it is considered a subcategory of idiopathic short stature (ISS) and indeed in younger children (less than 13 years), this condition cannot be differentiated from ISS. CDGP is characterised by a significant delay in both bone age and adolescent growth spurt, which underlies the transient short stature stage seen in affected individuals. GHSR (GH secretagogue receptor) gene, expressed in the hypothalamus and pituitary, is implicated in the aetiology of short stature. So far studies to identify candidate genes for this condition, have not targeted the GHSR gene .

Pugliese-Pires et al. investigated the presence of GHSR mutations in a group of ISS patients including a subgroup of patients with CDGP. They directly sequenced the GHSR coding region in 96 independent patients with ISS, 31 of them with CDGP, in 150 adults and in 197 children with normal stature. They report 5 new GHSR variations in patients with CDGP all of them absent in the large ethnically matched population. They hypothesise that in the presence of GHSR mutations, there is a decrease in ghrelin-mediated appetite, resulting in low BMI, which then contributes to a delayed onset of puberty.

Theirs is the first report of GHSR mutations in patients with CDGP and raise the intriguing possibility of an association between observed GHSR mutations and CDGP. Pugliese-Pires et al (2011) European Journal of Endocrinology 165 233-241.

Read the full article at DOI: 10.1530/EJE-11-0168.