[GHBP, IGF-1 and IGFBP-3 serum levels in familial short-statured and normal-statured children].

Background And Objective: Growth hormone binding protein (GHBP), insuline-like growth factor 1 (IGF-1) and insuline-like growth factor binding protein 3 (IGFBP-3) serum concentrations were studied in familial short-statured patients (FSS) and age-matched normal-statured subjects. The aim of the study was to ascertain whether differences in growth factors concentrations between groups could be shown and whether they may contribute to explaining the different patterns of growth in both groups.

Subjects And Method: Serum samples of 38 FSS patients (20 boys) and 31 normal-statured subjects (15 boys) in Tanner I stage (prepubertal), were analysed in a central laboratory.

A novel dysfunctional growth hormone variant (Ile179Met) exhibits a decreased ability to activate the extracellular signal-regulated kinase pathway.

The pituitary-expressed GH1 gene was screened for mutation in a group of 74 children with familial short stature. Two novel mutations were identified: an Ile179Met substitution and a -360A-->G promoter variant. The Ile179Met variant was shown to exhibit a similar degree of resistance to proteolysis as wild-type GH, indicating that the introduction of Met does not cause significant misfolding.