Objective: The term idiopathic short stature (ISS) describes children: (a) whose height is more than two standard deviations below the mean; (b) with normal or slow height velocity; (c) of normal birth weight; (d) showing an absence of specific endocrine abnormalities; and (e) having no evidence of chronic physical or psychological illness. It has been suggested that partial growth hormone (GH) insensitivity due to heterozygous mutations of the GH Receptor gene may account for some cases of ISS.
Design and methods: GHR gene was investigated (SSCP assay and direct sequencing) in 37 ISS patients. Fifty controls were recruited from the same geographic area as the patients; age and gender were stratified to match controls to patients.
Results: We observed the previously described transition A>G (GGA>GGG) of position 3 of codon 168, determining the synonymous change G168G in 22 of 37 patients (12 homozygous and 10 heterozygous) and in 23 of 50 controls (16 homozygous and 7 heterozygous). The relative allele frequency was similar in patients and in controls. In one ISS patient we identified a novel transition T>C (TGT>TGC) of position 3 of codon 94 , determining the synonymous change C94C. In another patient we demonstrated a novel heterozygous transition T>C (GTC>GCC) of the position 2 of codon 144, determining the missense mutation V144A, These mutations were not found in 100 control chromosomes.
Conclusions: Heterozygous mutations of the GHR gene are uncommon in Italian ISS patients, who are selected for adequate GH levels. However the observed incidence of 2 mutations out of 37 ISS patients (i.e., 5%) is not different from the one previously reported in the literature.