Ghrelin and growth hormone secretagogue receptor (GHSR) genes are not commonly involved in growth or weight abnormalities in an Israeli pediatric population.

Context and objective: Ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), have key roles in appetite control and growth regulation. To date, only few mutations of GHSR have been identified in children with obesity and short stature. We hypothesized that mutations in ghrelin or GHSR will result in disrupted growth and weight regulation in children. Design: A total of 98 subjects (38 females and 60 males) were enrolled with failure to thrive (FTT) (n=9), GH deficiency (GHD) (n=44), idiopathic short stature (ISS) (n=22) or obesity (n=23). The coding exons of both ghrelin and GHSR genes were screened for mutations by sequencing. Results: Seven different sequence changes were identified in GHSR, two of them novel and five described previously. One previously described sequence change (p.L72M) in the ghrelin gene was identified in five patients; however, the same variant was identified at a higher rate in controls. A high rate of sequence changes was shown in ghrelin and its receptor, GHSR, in our population, but none of these changes affected the coding region of the protein. Conclusions: Despite the major role of ghrelin in growth and appetite regulation, our results indicate that mutations in ghrelin and GHSR do not explain short stature and weight regulation disorders in children in our population.