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Familial Mediterranean fever (FMF) is an autosomal recessive disease mostly frequent in Mediterranean populations. Over 50 mutations have been identified in the gene responsible for the disease, MEFV. The present study reports the frequencies of MEFV mutations in 558 Lebanese and 55 Jordanian FMF patients and points out the severity of the M694V frequently observed mutation among these patients. Three novel mutations, T177I, S108R and E474K were also identified in the Lebanese group. An excess of homozygotes and a deficit of heterozygotes were observed in both samples when compared to the expected number of observed genotypes under the Hardy-Weinberg hypothesis. Homozygotes for M694V and M694I were still in excess in the Lebanese group of patients, even after consanguinous homozygotes were removed, or population structure was considered. This excess is therefore neither due to consanguinity nor to subgroups in the Lebanese population, but rather to more remote consanguinity or to a selection bias favoring the census of these genotypes. The fact that FMF female patients were less censed than male patients may be due to the greater resistance of females to pain and to the possibility of confusing abdominal and gynecological pain. The phenotypic heterogeneity of the FMF could then originate both from genetic causes like allelic heterogeneity or modulating genes, and cultural background facing the physiological consequences of genotypes at risk.

Familial Mediterranean fever (FMF) is an autoinflammatory autosomal recessive disease characterized by recurrent fever crises and serous inflammation. The MEFV gene responsible for the disease was identified on chromosome 16, and 5 of the mutations discovered so far in the gene are most frequently encountered in FMF patients: p.[M694V], p.[V726A], p.[M680I] and p.[M694I] in exon 10, and p.[E148Q] in exon 2. The present work describes multiple MEFV mutations and the corresponding haplotypes for 31 FMF patients as well as 32 "healthy" individuals of a large consanguineous Lebanese family. The DNAs were screened for MEFV mutations, and determination of the corresponding haplotypes was performed for all individuals by genotyping 4 microsatellites surrounding the gene. Five different mutations were detected in this one family, which is unexpected in such a genetic isolate. A phenotypic variability was also observed. The haplotype carrying the p.[M694I] allele, detected in all the family branches, was well conserved and therefore seems to be the ancestral one.

Background Familial Mediterranean fever (FMF) is an autosomal recessive disease mainly affecting particularly Arabs, Non-Ashkenazi Jews, Armenians, and Turks. It is an autoinflammatory periodic disorder characterized by febrile and painful attacks due to inflammation involving the serosal membranes in the abdomen, chest or joints. Over 50 mutations have been identified in the MEFV gene responsible for FMF. Objective To identify the distribution and the frequency of the MEFV gene mutations in Syrian FMF patients and population and perform a genotype/phenotype correlation in the patients' cohort. Patients and methods The study was carried out on 83 clinically diagnosed Syrian FMF patients and 242 healthy subjects. The tested individuals were screened for the most common five MEFV mutations (M694V, M694I, M680I, V726A and E148Q) by restriction fragment length polymorphism. Sequencing of exon 10 was performed only for the patients' DNA where just one or no mutation was detected. Results and discussion Of the 83 patients studied, 74 (89%) were positive either for one, two or three mutations and nine (11%) had no mutations detected. Of those positive for mutations, 25 were homozygous, 30 were compound heterozygotes, three had complex alleles, and 16 patients had only one mutation. The M694V, V726A, M694I, M680I and E148Q mutations accounted for 45.8%, 26%, 13.9%, 4.8% and 6% of the alleles, respectively. The carrier rate in the Syrian population for the tested mutations was 17.5%, E148Q being the most common mutation, followed by V726A and M694V. The severity of the disease and development of amyloidosis seem to have an association with M694V, the most common mutation in Syrian FMF patients.