Open Access Highly Accessed Research article

LIN28B, LIN28A, KISS1, and KISS1R in idiopathic central precocious puberty

Johanna Tommiska12*, Kaspar Sørensen3, Lise Aksglaede3, Rosanna Koivu12, Lea Puhakka12, Anders Juul3 and Taneli Raivio12

Author Affiliations

1 Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland

2 Children's Hospital, Helsinki University Central Hospital (HUCH), Helsinki, Finland

3 Department of Growth and Reproduction, Copenhagen University Hospital, DK-2100 Copenhagen, Denmark

For all author emails, please log on.

BMC Research Notes 2011, 4:363  doi:10.1186/1756-0500-4-363

Published: 22 September 2011

Abstract

Background

Pubertal timing is a strongly heritable trait, but no single puberty gene has been identified. Thus, the genetic background of idiopathic central precocious puberty (ICPP) is poorly understood. Overall, the genetic modulation of pubertal onset most likely arises from the additive effect of multiple genes, but also monogenic causes of ICPP probably exist, as cases of familial ICPP have been reported. Mutations in KISS1 and KISSR, coding for kisspeptin and its receptor, involved in GnRH secretion and puberty onset, have been suggested causative for monogenic ICPP. Variation in LIN28B was associated with timing of puberty in genome-wide association (GWA) studies. LIN28B is a human ortholog of the gene that controls, through microRNAs, developmental timing in C. elegans. In addition, Lin28a transgenic mice manifest the puberty phenotypes identified in the human GWAS. Thus, both LIN28B and LIN28A may have a role in pubertal development and are good candidate genes for monogenic ICPP.

Methods

Thirty girls with ICPP were included in the study. ICPP was defined by pubertal onset before 8 yrs of age, and a pubertal LH response to GnRH testing. The coding regions of LIN28B, LIN28A, KISS1, and KISS1R were sequenced. The missense change in LIN28B was also screened in 132 control subjects.

Results

No rare variants were detected in KISS1 or KISS1R in the 30 subjects with ICPP. In LIN28B, one missense change, His199Arg, was found in one subject with ICPP. However, this variant was also detected in one of the 132 controls. No variation in LIN28A was found.

Conclusions

We did not find any evidence that mutations in LIN28B or LIN28A would underlie ICPP. In addition, we confirmed that mutations in KISS1 and KISS1R are not a common cause for ICPP.

Keywords:
LIN28B; LIN28A; KISS1; KISS1R; idiopathic central precocious puberty; timing of puberty