Diagnostica molecolare dei disturbi dell'accrescimento: Il recettore del GH

Translated title of the contribution: Molecular diagnosis in growth defects: The GH receptor

E. Bonioli, S. Costabel, A. Di Stefano, D. Coviello, A. Citana, M. Tarò, A. Naselli, E. Di Battista, M. Vignolo, R. Gastaldi, G. Aicardi

Research output: Contribution to journalArticlepeer-review


The GH insensitivity (GHI) syndrome is an autosomal recessive condition characterised by resistance to the physiological action of GH. Homozygous mutations of the GH receptor (GHR) gene result in Laron syndrome, which is now classified as GH partial and total insensitivity. Heterozygous GHR mutations were found in patients with short stature, normal GH secretion, low serum concentrations of GH binding protein and IGF-1 and low growth rate; however the incidence of these mutations is lower if the subjects are selected on the basis of short stature and normal GH secretion. Mutations of the extracellular domain (exons 4,6,7) and a missense mutation in the intracellular domain (exon 10) have been described. From the molecular point of view the occurrence of GHI in patients with heterozygous mutations is not easily explained. Signal transduction of GH is initiated by the binding of a single GH molecule to its receptor, followed by GHR dimerization. A specific cytoplasmic residue is required for the internalisation and degradation of the GHR. The homodimers of two full-length wild-type GHR would usually be internalised and would transduce the GH signal into cells. In contrast, mutant receptors that lack these sequences would not be internalised and they would be expected to accumulate on the cell surface. The homodimers of two mutant GHR or the heterodimers composed of mutant GHR and wild GHR could compete with wild/wild GHR for the binding of GH. Overexpression may provide a generalised mechanism by which truncated cell-surface receptors exert their inhibitory effects of the normal GHR in a dominant negative manner. The size of the phenotypic effect likely derives from the degree of expression of the mutant protein compared to that of the wild-type protein. The diagnosis of heterozygous GHR mutations in ISS children is helpful in evaluating the natural history of the defect, in providing genetic counseling and eventually in planning GH treatment.

Translated title of the contributionMolecular diagnosis in growth defects: The GH receptor
Original languageItalian
Pages (from-to)40-45
Number of pages6
Issue number1
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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