• PMID: 24031091
• Gene Name: PROKR2
• Condition: Hypogonadotropic hypogonadism, Kallmann syndrome
• Association: The great prevalence of PROKR2 mutations in Maghrebian patients has practical consequences for molecular diagnosis of thedisease and genetic counseling in the Maghrebian population.
• Population size: 832
• Population details: 832 (120 presumably unrelated Maghrebian patients, 712 European patients)
• Sex: Male, Female
• Infertility type: Male infertility, Female infertility
• Associated genes: KAL1, FGFR1, FGF8, PROKR2, and PROK2
• Other associated phenotypes: Hypogonadotropic hypogonadism, Kallmann syndrome

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

Sarfati J, Fouveaut C, Leroy C, Jeanpierre M, Hardelin JP, Dodé C.

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. FAU - Sarfati, Julie AU - Sarfati J AD - Département de Génétique et Développement, Institut Cochin, Inserm U1016, Université Paris-Descartes, Paris, France. FAU - Fouveaut, Corinne AU - Fouveaut C FAU - Leroy, Chrystel AU - Leroy C FAU - Jeanpierre, Marc AU - Jeanpierre M FAU - Hardelin, Jean-Pierre AU - Hardelin JP