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: Delanie Bulcão Macedo, Letícia Ferreira Gontijo Silveira, Danielle Souza Bessa, Vinicius Nahime Brito, Ana Claudia Latronico
• Journal: Endocrine development (Endocr Dev) Vol. 29 Pg. 50-71 ( 2016) ISSN: 1662-2979 [Electronic] Switzerland
• PMID: 26680572 (Publication Type: Journal Article, Review)
• Copyright: © 2016 S. Karger AG, Basel.

Topics

• Adolescent
• Child
• Female
• Gonads (physiopathology)
• Humans
• Male
• Puberty, Precocious (genetics, physiopathology)