title: A GPR54-activating mutation in a patient with central precocious puberty.
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.
authors.affiliation: Developmental Endocrinology Unit, Medical Investigation Laboratory, Clinicas Hospital, São Paulo University Medical School, São Paulo.
authors.forename: Milena Gurgel
authors.initials: MG
authors.lastname: Teles
authors.forename: Suzy D C
authors.initials: SD
authors.lastname: Bianco
authors.forename: Vinicius Nahime
authors.initials: VN
authors.lastname: Brito
authors.forename: Ericka B
authors.initials: EB
authors.lastname: Trarbach
authors.forename: Wendy
authors.initials: W
authors.lastname: Kuohung
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Seminara
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.forename: Ursula B
authors.initials: UB
authors.lastname: Kaiser
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000595:Amino Acid Sequence; D002648:Child; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D059648:Kisspeptins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017354:Point Mutation; D011629:Puberty, Precocious / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000074502:Receptors, Kisspeptin-1; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; C106628:KISS1 protein, human; C118688:KISS1R protein, human; D059648:Kisspeptins; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D025521:Tumor Suppressor Proteins; D048049:Extracellular Signal-Regulated MAP Kinases