Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1

J Androl. 2009 Jan-Feb;30(1):41-5. doi: 10.2164/jandrol.108.005314. Epub 2008 Aug 21.


Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. To date, 4 different genes have been identified as responsible for the presence of KS; however, in many cases no mutations have been found in any of these genes. Herein, we report the molecular findings regarding the analysis of fibroblast growth factor receptor 1 (FGFR1), prokineticin receptor 2 (PROKR2), and prokineticin (PROK2) in patients with KS. Twenty-four patients with KS were studied in whom mutations in KAL1 had been investigated previously. Polymerase chain reaction products from FGFR1, PROKR2, and PROK2 were sequenced and mutations were sought in the open reading frame of the 3 genes. Two patients presented a heterozygous T-to-G transversion in exon 2 (c.518T>G) of the PROKR2, which results in a leucine-to-arginine substitution at codon 173. Our results strengthen the hypothesis of possible digenic inheritance in some patients with KS. Likewise, our data extend previous reports demonstrating that PROKR2 plays a role in the etiology of this syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • DNA Mutational Analysis
  • Extracellular Matrix Proteins / genetics*
  • Gastrointestinal Hormones / genetics*
  • Humans
  • Kallmann Syndrome / genetics*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics*
  • Neuropeptides / genetics*
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics*
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Peptide / genetics*
  • Young Adult


  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • Gastrointestinal Hormones
  • Nerve Tissue Proteins
  • Neuropeptides
  • PROK2 protein, human
  • PROKR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1