A GPR54-activating mutation in a patient with central precocious puberty

Author(s)

Teles, Milena Gurgel ; Bianco, Suzy D. C. ; Brito, Vinicius Nahime ; Trarbach, Ericka B. ; Kuohung, Wendy ; Xu, Shuyun ; Seminara, Stephanie B. ; Mendonca, Berenice B. ; Kaiser, Ursula B. ; Latronico, Ana Claudia ^[10]

• Document type: Journal article
• Source: New England Journal of Medicine; v. 358, n. 7, p. 709-715, Feb. 2008.
• Field of knowledge: Health Sciences - Medicine

Abstract

Gonadotropin-dependent, or central, precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. In girls, this condition is most often idiopathic. Recently, a G protein-coupled receptor, GPR54, and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). In this study, we have identified an autosomal dominant GPR54 mutation - the substitution of proline for arginine at codon 386 (Arg386Pro) - in an adopted girl with idiopathic central precocious puberty (whose biologic family was not available for genetic studies). In vitro studies have shown that this mutation leads to prolonged activation of intracellular signaling pathways in response to kisspeptin. The Arg386Pro mutant appears to be associated with central precocious puberty. (AU)

• FAPESP's process: 05/04726-0 - Molecular characterization of congenital endocrine diseases that affect growth and development
• Grantee: Ana Claudia Latronico Xavier
• Support Opportunities: Research Projects - Thematic Grants