@misc{aiello_cirillo_cassio_mase_tornese_umano_giudice_grandone_2020, 
  title={Molecular Screening of PROKR2 Gene in Girls with very early Idiopathic Central Precocious Puberty.}, 
  DOI={10.21203/rs.3.rs-41264/v1}, 
  abstractNote={<jats:title>Abstract</jats:title>
        <jats:p><jats:bold>Background </jats:bold>Prokineticin receptor 2 (<jats:italic>PROKR2</jats:italic>) 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.<jats:bold>Methods </jats:bold>We analyzed DNA of 31 girls with idiopathic CPP diagnosed via basal LH levels &gt; 0.3 IU/L or peak-LH &gt; 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.<jats:bold>Results </jats:bold>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).<jats:bold>Conclusions </jats:bold>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.</jats:p>}, 
  publisher={Research Square}, 
  author={Aiello, Francesca and Cirillo, Grazia and Cassio, Alessandra and Mase, Raffaella Di and Tornese, Gianluca and Umano, Giuseppina Rosaria and Giudice, Emanuele Miraglia del and Grandone, Anna}, 
  year={2020}, 
  month={Jul}
  }