MEFV gene allele frequency and genotype distribution in 3230 patients’ analyses by next generation sequencing methods

Familial Mediterranean Fever (FMF, OMIM ID: 249100) is the most common autoinflammatory, autosomal recessive disease caused by mutations in the MEFV gene. It is widespread in the Mediterranean, primarily among Turkish, Armenian, Arab and Jewish. This study aims to examine genotype distributions of common MEFV variants in the Turkish population using targeted NGS and to evaluate all rare mutations. It included 3230 people applying to Ege University Children's Hospital Molecular Medicine Laboratory with the suspicion of autoinflammatory disease between 2017 and 2021. MEFV missense variant was detected in 1839 (56.9%) individuals. One or more mutations were found in them. 1063 patients were heterozygous (57.8%), 410 were compound heterozygous (22.3%), 238 were complex genotype (12.9%), and 128 were homozygous (7%). 56 different mutations and 141 genotypes were detected, two of which were novel (p.His87Arg, c.260A > G and p.Leu396Phe, c.1186C > T). These were determined as 6benign, 40 uncertain significant, 3 likely pathogenic and 7 pathogenic according to the ACMG classification. The most common ones were R202Q (n = 1097, 37.48%), E148Q (n = 512, 17.49%), M694V (n = 493, 16.84%), V726A (n = 155, 5.30%), M680I (n = 150, 5.12%), P369S (n = 108, 3.69%), R408Q (n = 95, 3.25%) respectively. They constitute 89.17 % of the entire patient population. In conclusion, DNA variants/mutations in the MEFV gene were evaluated in 3230 patients. To date, no mutation screening has been encountered in such a large population using NGS. Genotype distributions of both common and rare mutations were revealed. The obtained data will hopefully contribute to the future genotype-phenotype studies of FMF disease.