Familial Mediterranean fever: prevalence, penetrance and genetic drift

FMF is widely distributed in populations inhabiting the Mediterranean basin . It is mainly attributed to five founder mutations (M680I, M694V, M694I, V 726A, E148Q) in the MEFV gene. The frequencies and distribution of these mu tations in 146 FMF patients, of Arab and Jewish descent, were compared to t hat observed in 1173 healthy individuals of pertinent ethnic groups. Five m utations accounted for 91% of FMF chromosomes in our patients. Mutation M69 4V, predominant in North African Jews, was observed in all patients other t han Ashkenazi Jews; mutation V726A was prevalent among all patients other t han North African Jews; mutations M6941 and M6801 were mainly confined to A rab patients. Overall carrier rates, for four mutations (M6801, M694V, V726 A, E148Q), were extremely high in our healthy cohort composed of Ashkenazi (n=407); Moroccan (n=243); Iraqi Jews (n=205); and Muslim Arabs (n=318); ca lculated at 1:4.5; 1:4.7; 1:3.5 and 1:4.3 respectively. The V726A allele pr evalent among Ashkenazi and Iraq! Jews and Muslim Arabs (carrier rates: 7.4 , 12.8 and 7.3%, respectively) was not found among Moroccan Jews. The M694V allele detected among Moroccan and Iraqi Jews and Muslim Arabs (carrier ra tes 11.1, 2.9 and 0.6%, respectively) was not observed among Ashkenazim. Th e overall frequency of mutations V726A and E148Q in Ashkenazim, Iraqi Jews and Arabs indicates that the bulk of individuals that comply with the genet ic definition of FMF remain asymptomatic.