Molecular Screening of PROKR2 Gene in Girls with very early Idiopathic Central Precocious Puberty

Background Prokineticin receptor 2 (PROKR2) loss of function mutations have been described as cause of hypogonadotropic hypogonadism. In 2017 a first case of central precocious puberty (CPP) caused by heterozygous gain of function mutation in PROKR2 was described in a 3.5-year‐old girl. No other cases have been reported yet. This study performs a molecular screening in girls with “early” onset CPP (breast budding before 6 years of age) in order to identify possible alterations in PROKR2.Methods We analyzed DNA of 31 girls with idiopathic CPP diagnosed via basal LH levels > 0.3 IU/L or peak-LH > 5UI/L after stimulation, negative for MKRN3 mutations. The Fisher exact test was used to compare allele frequency of polymorphism found to Exome Aggregation Consortium (ExAC) dataset.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 similar to that reported in literature. rs3746682 presented a minor allele frequency higher than described in The Exome Aggregation Consortium (ExAC) (0.84 in our population vs 0.25 from ExAC).Conclusions As for other G-protein-coupled receptors (i.e. GPR54), mutations in PROKR2 do not seem to be a frequent cause of CPP in girls.