Familial Mediterranean fever gene mutation frequencies and genotype–phenotype correlations in the Aegean region of Turkey

Abstract

Familial Mediterranean fever (FMF) is a disease characterized by recurrent, self-limiting fever and serositis and caused by altered pyrin due to mutated MEFV gene. The aim of this study was to investigate clinical manifestations and MEFV mutations among patients with FMF and healthy controls in the Aegean region of Turkey. This study included 308 patients and 164 healthy controls. Patients were divided into three groups according to Tel-Hashomer criteria; definitive, probable, and suspicious. Among the patients, 146 were women (47.4%) and 162 were men (52.6%). The mean age (±SD) of the patients at the diagnosis was 9.6±3.95 (range 0.5-18). The mean age (±SD) at onset of the symptom was 6.2±3.95 (range 1-18). Symptoms were seen earlier onset in definitive group than the suspicious group in our cohort (4.7±3.9 years, 6.6±3.9 years, respectively; P=0.001). Clinical features were abdominal pain (83.1%), fever (55%), arthritis (17.1%), myalgia (4.5%), pleuritis (10%), and erysipelas-like erythema (7.7%). Fever, arthralgia, arthritis, chest pain, and amyloidosis were found statistically significant more in definitive group than suspicious group (P<0.001, P<0.001, P<0.001, P<0.05, and P<0.001, respectively). MEFV gene mutations were identified in 199 patients (64.6%). The most commonly encountered MEFV mutation among the patients was M694V homozygote (25%). M694V homozygous mutation was found most frequently in definitive FMF group than other groups (49, 9, 8.9%, respectively). To our knowledge that FMF should be suspected in the case of non-specific but recurrent attacks of serositis and high fever, and molecular analysis should be performed in order to make diagnosis of FMF.

Genotype and Phenotype Correlations in Children with Familial Mediterranean Fever

“…The majority of the patients in the present study (n=158 [84%]) had a moderate severity score, and the mean disease severity score was significantly higher in the M694V homozygote group and compound heterozygote group than in the group with no mutation (p=0.001 and p=0.048, respectively), whereas there was no significant difference between the M694V homozygote and M694V heterozygote groups (p=0.132). These findings might indicate that patients with homozygote M694V mutation and compound heterozygote mutation have a more severe disease course, as previously reported (11,23). Nonetheless, as the Pras scoring system is designed for adults, we are aware that there may be some inconsistencies when it is used with children.…”

The Effect of M694V Mutation on Clinical Presentation and Acute Phase Response in Children with Familial Mediterranean Fever: Single Center Experience in Western Turkey

“…2,9,11 Re cently, in a lar ge co hort study from the Ae ge an re gi on of Tur key, the M694V ho mozy go us mu ta ti on was fo und most frequ ently in a de fi ni ti ve FMF gro up, ba sed on TelHas ho mer cri te ri a. 26 In Wes tern re gi on of Tur key, we fo und that M694V ho mozy go te mu ta ti on was as so ci a ted with a se ve re cli ni cal co ur se whe re as E148Q mu ta ti on was as so ci a ted with a pre fe rab le cli ni cal co ur se. Ear li er age at onset of di se a se, higher fre qu en ci es of art hri tis, ery si pe las-li ke ery thema and myal gi a, hig her at tack ra te and se ve rity sco re, low res pon se ra te to colc hi ci ne tre at ment, and hig her le vels of WBC, CRP and ESR du ring attack-pe ri od we re as so ci a ted with the pre sen ce of M694V mu ta ti on in our study.…”

Homozygous M694V as a risk factor for amyloidosis in Turkish FMF patients

“…We analyzed twenty-seven papers (Akpolat et al, 2010;Albayrak, 2010;Atagunduz et al, 2004;Cakar et al, 2001;Delibaş et al, 2005;Duşunsel et al, 2008;Erdağ et al, 2008;Ertekin et al, 2005;Inal et al, 2009;Ozalkaya et al, 2011;Oztürk et al, 2008;Koksal et al, 2009;Mimouni et al, 2000;Pasa et al, 2008;Peru et al, 2008;Samli et al, 2006;Sayhan et al, 2000;Shohat et al, 1998Shohat et al, , 1999Solak et al, 2008;Soylemezoglu et al, 2010;Turkcapar et al, 2007;Ureten et al, 2010;Yalçinkaya et al, 2000;Yilmaz et al, 2001;Yilmaz et al, 2003;Yigit et al, 2008) from 20 centers located in 11 different cities and including 3505 subjects (400 with amyloidosis and 3105 without amyloidosis). The data of one center (Center 20) which did not publish their cases separately was obtained from an international study (Mimouni et al, 2000) (online Supplementary data).…”