Introduction: PROKR2 is a 384-amino acid G-protein-coupled receptors (GPCR) that regulates GnRH secretion in the hypothalamus. PROKR2 mutations have been described as cause of a certain percentage of of hypogonadotropic hypogonadism and Kallmann syndrome.
In 2017 a heterozygous frameshift gain of function mutation of PROKR2 was identified in a 3.5-year-old girl with central precocious puberty (CPP).
The aim of our study was to perform a mutation screening of such gene in girls with "early" onset CPP (first signs of puberty occurred ≤ 6 years of age).
Materials and Methods: We enrolled 25 girls with idiopathic CPP with pubertal basal LH level or pubertal LH response to GnRH testing (mean age at first observation 5.5 years, range 2-7; mean age at first occurrence of thelarche 5 years old, range 1-6).
Results: No rare variants were identified. Five polymorphisms were found (rs6076809, rs8116897, rS3746684, rs3746682, rs3746683). All except one (i.e. rs3746682) had a minor allele frequency (MAF) similar to that reported in literature. rs3746682 presented a MAF higher than described in The Exome Aggregation Consortium (ExAC) (0.84 in our population vs 0.25 from ExAC).
Conclusions: Our data suggest that mutations in PROKR2 gene are not a frequent cause of central precocious puberty in girls, even in subjects with a very early onset CPP. As for other G-protein-coupled receptors (i.e. GPR54), gain of function mutations affecting these kind of hypothalamic regulating factors are a very rare cause of CPP in girls. The significance of the different MAF of rs3746682 polymorphism has to be investigated in larger samples of patients and controls.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology