Molecular Screening of PROKR2 Gene in Girls with Idiopathic Central Precocious Puberty.
Abstract Background: Prokineticin receptor 2 (PROKR2) loss of function mutations have been describedas cause of hypogonadotropic hypogonadism. In 2017, a first case of central precocious puberty(CPP) caused by PROKR2 heterozygous gain of function mutation was described in a 3.5 years-oldgirl. No other cases have been reported yet. This study performs a molecular screening ingirls with early onset CPP (breast budding before 6 years of age) to identify possiblealterations in PROKR2.Methods: We analysed DNA of 31 girls with idiopathic CPP diagnosed via basal LH levels >0.3IU/L or peak-LH>5IU/L after stimulation, without any MKRN3 mutations. The Fisher exact test was used to compare polymorphism allele frequency to corresponding ones in genome aggregation database (gnomAD).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 that described in the gnomAD (0.84 in our cohort vs 0.25 from gnomAD).Conclusions: As for other G protein-coupled receptors (i.e. GPR54), mutations in PROKR2 donot seem to be a frequent cause of CPP in girls.