A comprehensive molecular analysis and genotype-phenotype correlation in patients with familial mediterranean fever

Familial Mediterranean fever is an auto inflammatory genetic disease involving especially Turks, Armenians, Arabs and non-Ashkenazi Jews and caused by variants in the MEFV gene. In this study, we aimed to evaluate the distribution and frequency of clinical, MEFV gene variants in FMF patients and the relationship between mutations in different exons and phenotype-genotype and clinical findings. 1028 patients diagnosed as FMF were included. The most common genotypes were M694V / R202Q heterozygous (10.4%), M694V homozygous (7.5%), M694V / E148Q / R202Q heterozygous (4.6%), V726A heterozygous (4.5%), M680I heterozygous (4.2%). c.1611-1 G > C, G152R, S104C, R116S, E336K, R461Q mutations were detected in the literature for the first time in FMF patients. We also divided the patients into 4 groups according to whether the MEFV mutations were exon 10 or non-exon 10. The first group consisted of non-exon 10 homozygous or compound heterozygous (n = 180) patients, Group 2 consisted of exon 10- non-exon 10 compound heterozygous (n = 318) patients, Group 3 consisted of exon 10 homozygous or compound heterozygous (n = 256) patients, while Group 4 consisted of heterozygous (n = 227) patients at any exon. There was no significant difference between the groups in terms of abdominal pain, arthritis, arthralgia, vomiting diarrhea, erysipelas like rash, amyloidosis, renal failure family history. There was no difference in fever between Group 1 (55.6%) and 2 (62.3%); however, these two groups were different from Group 3 (75.8%) and 4 (76.7%). Group 3 (18.8%) had the highest rate of appendectomy. In addition, allele frequencies of all mutations detected in the analyses were compared with allele frequencies of healthy people in the gnomad database. It is useful to analyse all exons in the MEFV gene with the next generation sequence analysis in the detection of FMF disease. S104C, R116S, G152R, E336K, R461Q, L508Q and c.1611-1 G > C mutations are also new variants in literature. c.1611-1 G > C is a possible pathogenic variant.