title: Greater prevalence of PROKR2 mutations in Kallmann syndrome patients from the Maghreb than in European patients.
abstract: BACKGROUND
  Kallmann syndrome (KS) is a genetically heterogeneous developmental disorder that associates hypogonadotropic hypogonadism and anosmia. Various causative genes have been identified, but their respective involvement in different world regions is poorly documented.
  
  
  OBJECTIVE
  We aimed to compare the prevalence of mutations in five routinely analyzed KS genes between Maghrebian and European patients.
  
  
  METHODS
  Blood samples from 120 presumably unrelated Maghrebian patients were collected for DNA sequencing by the Sanger technique. The prevalence of the non-synonymous mutations in KAL1, FGFR1, FGF8, PROKR2, and PROK2 was determined for each gene, and compared with those previously obtained from the analysis of 712 European patients.
  
  
  RESULTS
  Diverse mutations in PROKR2, a gene involved both in monogenic recessive and digenic/oligogenic KS transmission modes, were found in 23.3% of the Maghrebian patients, but only in 5.1% of the European patients (Fisher's exact test, P<0.001), whereas mutations in each of the other four KS genes were present either at similar frequencies in the Maghrebian and European patients (KAL1, PROK2, FGF8, from 6.6 to 0.8%; Fisher's exact test, P>0.4 for all comparisons) or at a lower frequency in Maghrebian patients (FGFR1, 5.0 vs 11.7%; Fisher's exact test, P<0.05). Homozygosity resulting from consanguineous marriages was not sufficient to account for the greater prevalence of PROKR2 mutations in the Maghrebian patients.
  
  
  CONCLUSIONS
  The great prevalence of PROKR2 mutations in Maghrebian patients has practical consequences for molecular diagnosis of the disease and genetic counseling in the Maghrebian population.
authors.affiliation: Département de Génétique et Développement, Institut Cochin, Inserm U1016, Université Paris-Descartes, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Sarfati
authors.forename: Corinne
authors.initials: C
authors.lastname: Fouveaut
authors.forename: Chrystel
authors.initials: C
authors.lastname: Leroy
authors.forename: Marc
authors.initials: M
authors.lastname: Jeanpierre
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hardelin
authors.forename: Catherine
authors.initials: C
authors.lastname: Dodé
mesh_terms: D000328:Adult; D000352:Africa, Northern; D000368:Aged; D018912:Arabs / Q000235:genetics*; D005060:Europe; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics; D005768:Gastrointestinal Hormones / Q000235:genetics; D005787:Gene Frequency; D006801:Humans; D007438:Introns; D017436:Kallmann Syndrome / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D015995:Prevalence; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics*
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; C496456:FGF8 protein, human; D005768:Gastrointestinal Hormones; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C423608:PROK2 protein, human; C470838:PROKR2 protein, human; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D051524:Fibroblast Growth Factor 8; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1