Familial Mediterranean fever in the Syrian population: gene mutation frequencies, carrier rates and phenotype-genotype correlation.

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.