Background Familial Mediterranean fever (FMF) is the first diagnosed, most frequent and best known of the hereditary periodic fever syndromes. FMF is characterized with self limiting relapsing fever and serousitis attacks and inherited with an autosomal recessive pattern. MEFV mainly encodes a 781 amino acidic protein called as pyrin (or marenostrin). Recently, mutations over 150 are identified at MEFV. While four of the most prominent five mutations is on the 10th exon (M694V, M680I, M694I, V726A), the other is on the 2nd exon (E148Q). Clear effect of these mutations is an auto inflammatory state. With decrease at the anti inflammatory effect of pyrin or increase at the pro inflammatory signal; secondary to MEFV mutations; innocuous stimulations may result with inflammatory attacks. Predominant geographic distribution area of FMF is southern Caucasia, Anatolia and Middle East. Mostly affected ethnical groups from the disease are Turks, Arabs, Armenians and Jews.
Objectives In this study it is aimed to evaluate the ratio of MEFV gene mutations in Turkish FMF patients
Methods Study plan were sent to FMF centers in Turkey and they were invited to the study. Fifteen centers among ten various geographic distributions accepted to be included in the study. Patients fullfilling diagnostic criteria of Tel – Hashomer or Sheba Medical Center for FMF were included to the study (Pras E-1998, Livneh A-1997).MEFV mutations were investigated by polymerase chain reaction and reverse hybridization assay (FMF StripAssay; Vienna Lab Labordiagnostika GmbH, Vienna Austria) or pyrosequencing technique (Qiagen).
Results MEFV gene mutations of 1719 Turkish FMF patients were evaluated. Most frequent MEFV mutation was homozygous M694V. M694V +/+ 24%, M694V allele was present in all of the most common 5 MEFV mutations. Respectively, M694V +/+ (24%), M694V +/- (17%), M694V/M680I (8.4%), M694V/V726A (7.3%), M694V/E148Q (5.3%).Instead of negativity of MEFV mutations in 154 of the patients (9%), patients were diagnosed as FMF according to the concordance of clinical findings.
Conclusions According to the results, M694V was the most frequently observed mutation in our study (allelic frequency= %43.05). It is followed by M680I (%11.2), V726A (%5.79) and E148Q (%4.17). These were in accordance with the former nationwide FMF study in Turkey. Especially M694V homozygous patients have higher risk for amyloidosis and arthritis. These patients should be followed up closely. The ratio of MEFV mutation negative patients were found high. The reasons can be other mutations or other diseases that cannot be recognized.
Onen F. Familial Mediterranean fever. Rheumatol Int. 2006 Apr; 26(6):489-496.
Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore). 2005 Jan; 84(1):1-11.
Disclosure of Interest None declared