Greater prevalence of PROKR2 mutations in Kallmann syndrome patients from the Maghreb than in European patients

Eur J Endocrinol. 2013 Oct 21;169(6):805-9. doi: 10.1530/EJE-13-0419. Print 2013 Dec.

Abstract

Context: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Africa, Northern
  • Aged
  • Arabs / genetics*
  • Europe
  • Exons
  • Extracellular Matrix Proteins / genetics
  • Female
  • Fibroblast Growth Factor 8 / genetics
  • Gastrointestinal Hormones / genetics
  • Gene Frequency
  • Humans
  • Introns
  • Kallmann Syndrome / epidemiology
  • Kallmann Syndrome / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Nerve Tissue Proteins / genetics
  • Neuropeptides / genetics
  • Prevalence
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Peptide / genetics*
  • Sequence Analysis, DNA
  • White People / genetics*

Substances

  • ANOS1 protein, human
  • Extracellular Matrix Proteins
  • FGF8 protein, human
  • Gastrointestinal Hormones
  • Nerve Tissue Proteins
  • Neuropeptides
  • PROK2 protein, human
  • PROKR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Fibroblast Growth Factor 8
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1