Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Creek orthodoxes, Creek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M6941 mutations

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in th e MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G -- > C), M6801 (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2 using PCR digestion, ARMS, DGGE and/or sequencing . Mutations were detected in patients belonging to all communities, most in terestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M6941, E148Q and M6801 mutations accoun t respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutati ons was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations a t codon 694 in exon 10 (both M694V and M6941). None of the patients carryin g other mutations developed amyloidosis.