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

ContextKallmann 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.ObjectiveWe aimed to compare the prevalence of mutations in five routinely analyzed KS genes between Maghrebian and European patients.MethodsBlood samples from 120 presumably unrelated Maghrebian patients were collected for DNA sequencing by the Sanger technique. The prevalence of the non-synonymous mutations inKAL1,FGFR1,FGF8,PROKR2, andPROK2was determined for each gene, and compared with those previously obtained from the analysis of 712 European patients.ResultsDiverse mutations inPROKR2, 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,PKAL1,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,PPROKR2mutations in the Maghrebian patients.ConclusionsThe great prevalence ofPROKR2mutations in Maghrebian patients has practical consequences for molecular diagnosis of the disease and genetic counseling in the Maghrebian population.