Mutations in the MEFV gene in a large series of patients with a clinical diagnosis of familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessively inherited di sease affecting patients of the Mediterranean basin. FMF is characterized b y recurrent episodes of fever accompanied with topical signs of inflammatio n. Some patients can develop a renal amyloidosis associated (AA) amyloidosi s, The administration of colchicine is an effective preventive treatment of both the attacks and amyloidosis. The FMF gene (MEFV) was cloned and misse nse mutations were found to be responsible for the disease, We investigated a large series of 303 unselected and unrelated patients of various ethnic backgrounds with a clinical suspicion of FMF to confirm or invalidate the d iagnosis of FMF and to determine the spectrum of MEFV mutations. Molecular analysis focused on all the most frequent mutations identified so far, and an exhaustive analysis of exon 10, containing the mutational hotspot, was p erformed through DNA sequencing, Sixty-two percent of Sephardic, North Afri can Arabs, Armenian and Turkish patients were either homozygous or compound heterozygous for MEFV mutations, In other populations surrounding the Medi terranean Sea such as Creek, Italian, Portuguese, Kurdish and Lebanese popu lations, mutations were also found, In general, patients without Mediterran ean origin had no mutations in the MEFV gene, Two new missense mutations we re identified in exon 10 of the MEFV gene: the S675N in an Italian patient and the M680L in a French patient without any known at-risk ethnic ancestry . Am. J, Med, Genet, 92:241-246, 2000. (C) 2000 Wiley-Liss, Inc.