An update on the genetic causes of central precocious puberty

Abstract

Central precocious puberty (CPP) is caused by the premature reactivation of the hypothalamic-pituitary-gonadal axis. Genetic, nutritional, and environmental factors play a crucial role in determining pubertal timing. Recently mutations in kisspeptin (KISS1), kisspeptin receptor (KISS1R), and makorin RING finger protein 3 (MKRN3) genes have been identified as genetic causes of CPP. In particular, the MKRN3 gene is known to affect pubertal initiation. The MKRN3 gene is located on chromosome 15q11-q13 in the Prader-Willi syndrome (PWS) critical region. MKRN3 deficiency, due to a loss of function mutation, leads to the withdrawal of hypothalamic inhibition and prompts pulsatile gonadotropin-releasing hormone secretion, resulting in precocious puberty. The exact functions of these genes associated with CPP are still not well understood. Larger studies are required to discover the mechanisms involved in pubertal development.

Keywords: Central precocious puberty; Kisspeptins; MKRN3 gene; Mutation.

Fig. 1. MKRN3 domains (3 C3H zinc finger motifs, 1 C3HC4 RING zinc finger motif, and 1 MKRN specific Cys-His domain) and MKRN3 mutations identified in patients with central precocious puberty. The numbers correspond to the amino acid positions in the protein. 8 frameshift mutations (blue), 10 missense mutations (red) and 3 nonsense mutations (green) are shown.