Higher than expected carrier rates for familial Mediterranean fever in various Jewish ethnic groups

Familial Mediterranean fever (FMF) is an autosomal recessive disease charac terised by recurrent attacks of inflammation of serosal membranes. Amyloido sis leading to renal failure is the most severe complication in untreated p atients. In Israel FMF is most frequent among Jews of North African origin. Recently the causative gene (MEFV) has been found and the common mutations characterised. The aim of this study was to investigate the carrier rates of the common MEFV mutations among 400 healthy members of four different et hnic groups (100 in each group) in Israel, and to compare the distribution of the different mutations between FMF carriers and patients. We found a hi gh frequency of carriers among Jews from the various ethnic groups. In Nort h African Jews it was 22%, in Iraqi Jews 39%, in Ashkenazi Jews 21%, and in Iranian Jews 6%. The distribution of the four most common MEFV mutations a mong healthy individuals (M694V 29%, V726A 16%, M6801 2% and E148Q 53%) was significantly different (P < 0.003) from that found in patients (M694V 84. 4%, V726A 9.0%, M6801 0% and E148Q 6.6%). Six healthy asymptomatic individu als were found to carry mutations in both alleles: two homozygotes for E148 Q and four compound heterozygotes E148Q/other. These results demonstrate a very high carrier rate among all Jewish ethnic groups. They confirm that mu tation E148Q is associated with a milder phenotype, which explains the lowe r prevalence of FMF among the Ashkenazi and Iraqi Jews. This study raises t he question of the need for molecular screening for M694V homozygotes in th e Israeli North African Jewish community.