title: Sexual Precocity--Genetic Bases of Central Precocious Puberty and Autonomous Gonadal Activation.
abstract: Precocious puberty has been classically defined as the onset of sexual secondary characteristics in girls younger than 8 years and in boys younger than 9 years. The discovery of potential factors which trigger human puberty is one of the central mysteries of reproductive biology. Several approaches, including mutational analysis of candidate genes, large-scale genome-wide association studies, and (more recently) whole-exome sequencing, have been performed in attempt to identify novel genetic factors that modulate the human hypothalamic-pituitary-gonadal axis, resulting in premature sexual development. In the last two decades, it has been well established that autonomous gonadal activation can be caused by somatic (GNAS) or germline (LHCGR)-activating mutations of genes that encode essential elements for signal transduction of G protein-coupled receptors, resulting in peripheral precocious puberty in McCune-Albright syndrome and testotoxicosis, respectively. More recently, dominant activating and inactivating mutations of excitatory (KISS1/KISS1R) and inhibitory (MKRN3) modulators of gonadotropin-releasing hormone secretion, respectively, were associated with central precocious puberty phenotype. Indeed, loss-of-function mutations of MKRN3, a maternal imprinted gene located at chromosome 15q, currently represent a frequent cause of central precocious puberty diagnosed in families from distinct geographic origins. Here, we review the known genetic defects in central and peripheral precocious puberty.
authors.forename: Delanie Bulcão
authors.initials: DB
authors.lastname: Macedo
authors.forename: Letícia Ferreira Gontijo
authors.initials: LF
authors.lastname: Silveira
authors.forename: Danielle Souza
authors.initials: DS
authors.lastname: Bessa
authors.forename: Vinicius Nahime
authors.initials: VN
authors.lastname: Brito
authors.forename: Ana Claudia
authors.initials: AC
authors.lastname: Latronico
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006066:Gonads / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011629:Puberty, Precocious / Q000235:genetics* / Q000503:physiopathology*