Pathogenic and low frequency variants in children with central precocious puberty

Background Central precocious puberty (CPP) due to premature activation of GnRH secretion results in early epiphyseal fusion and to a significant compromise in the achieved final adult height.  CPP is usually idiopathic and is disproportionally observed in girls compared to boys. Currently, only few genetic determinants of children with CPP have been described and the role they exert on the development of the disorder. In this original study rare variants in MKRN3, DLK1, KISS1, KISS1R and MAGEL2 genes are reported in patients with CPP.

Methods Fifty-four index females and 2 index males with CPP underwent whole exome sequencing (WES) by Next Generation Sequencing (NGS). The identified rare variants were initially examined by in silico computational algorithms and confirmed by Sanger sequencing. Additionally, a genetic network for the MKRN3 gene mimicking a holistic regulatory depiction of the crosstalk between MKRN3 and other genes is designed.

Results Three previously described pa...