Recurrent nonsense mutations in the growth hormone receptor from patients with laron dwarfism

Serge Amselem, Marie Laure Sobrier, Philippe Duquesnoy, Raphaël Rappaport, Marie Catherine Postel-Vinay, Micheline Gourmelen, Bruno Dallapiccola, Michel Goossens

Research output: Contribution to journalArticlepeer-review

Abstract

In addition to its classical effects on growth, growth hormone (GH) has been shown to have a number of other actions, all of which are initiated by an interaction with specific high affinity receptors present in a variety of tissues. Purification of a rabbit liver protein via its ability to bind GH has allowed the isolation of a cDNA encoding a putative human growth hormone receptor that belongs to a new class of transmembrane receptors. We have previously shown that this putative growth hormone receptor gene is genetically linked to Laron dwarfism, a rare autosomal recessive syndrome caused by target resistance to GH. Nevertheless, the inability to express the corresponding full-length coding sequence and the lack of a test for growth-promoting function have hampered a direct confirmation of its role in growth. We have now identified three nonsense mutations within this growth hormone receptor gene, lying at positions corresponding to the amino terminal extremity and causing a truncation of the molecule, thereby deleting a large portion of both the GH binding domain and the full transmembrane and intracellular domains. Three independent patients with Laron dwarfism born of consanguineous parents were homozygous for these defects. Two defects were identical and consisted of a CG to TG transition. Not only do these results confirm the growth-promoting activity of this receptor but they also suggest that CpG doublets may represent hot spots for mutations in the growth hormone receptor gene that are responsible for hereditary dwarfism.

Original languageEnglish
Pages (from-to)1098-1102
Number of pages5
JournalJournal of Clinical Investigation
Volume87
Issue number3
Publication statusPublished - 1991

Keywords

  • Human growth hormone receptor
  • Laron dwarfism
  • Stop mutation

ASJC Scopus subject areas

  • Medicine(all)

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