Familial Mediterranean fever gene mutations in the Southeastern region of Turkey and their phenotypical features

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. Several studies have focused on the differences between frequency of the mutations and their phenotypical manifestations. The aim of this study was to evaluate whether or not this phenotypical variation is associated with the existence of particular mutations. Twelve MEFV (Mediterranean fever) gene mutations were investigated in 119 patients suffering from FMF. Heterozygote M694V (21/119), heterozygote E148Q (21/119), homozygote M694V (17/119) and heterozygote V726A (12/119) mutations were the most common mutations. Patients were grouped according to the presence of the M694V mutation: group I was M694V/M694V, group II was M694V/others, and group III was other/other. Mean severity scores for the groups were 13.94 +/- 4.10, 10.79 +/- 3.01 and 8.31 +/- 2.26, respectively. There were statistically significant differences between the mean severity scores of groups I and II (p = 0.029), groups I and III (p < 0.0001), and groups II and III (p < 0.0001). Diagnosis of amyloidosis was established in four (23%) patients of group I, and three (8%) patients of group II, but in none of the patients in group III. There was also a statistically significant difference between groups I and III (p = 0.046), but not between groups II and III (p = 0.083) and groups I and II (p = 0.317) in terms of amyloidosis development. In conclusion, we found a higher disease severity score and higher prevalence of amyloidosis in FMF patients who were M694V mutation carriers. Many ethnic groups live in Anatolia and more ethnic origin-based studies are needed to determine the real effect of these mutations on disease severity and amyloidosis.

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

“…1 Se ve ral stu di es from dif fe rent coun tri es as well as dif fe rent re gi ons of Tur key ha ve emp ha si zed that M694V ho mozy go us ge noty pe have a mo re se ve re form of di se a se ma ni fes ted by an ear li er age of on set, hig her fre qu ency of at tacks, hig her pre va len ce of art hri tis and ple u risy, hig her fre qu ency of amy lo i do sis and hig her se ve rity scores compared to the ot her ge noty pes. 2,11,[20][21][22][23][24][25] On the con trary, so me stu di es sho wed that the pre sen ce of M694V mu ta ti on was not fo und to be as so ci a ted with a se ve re form of the di se a se or the de ve lopment of amy lo i do sis. 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.…”

Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey

“…Five founding mutations M694V, V726A, M680I, M694I (in exon 10), and E148Q (in exon 2) are the most common MEFV mutations (Sarrauste De Menthière C, 2003;Milhavet et al, 2008). Several reports have shown that the M964V mutation is associated with severe disease featuring early onset, high frequency of attacks, the need for the high doses of colchicine and high frequency of amyloidosis in untreated patients (Saatçi et al, 1997;Mattitt et al, 2006;Düşünsel et al, 2008;Paşa et al, 2008;Jarjour, 2010). The syndrome also features high levels of erythrocyte sedimentation rate, C-reactive protein and serum amyloid A, but case-specific consensus on phenotype and genotype in FMF patients has not been reached (Aldea et al, 2004).…”

Mediterranean Fever Gene Mutations and Messenger Ribonucleic Acid Expressions in Pediatric Patients With Familial Mediterranean Fever in the Trakya Region of Turkey

“…[11][12][13][14][15][16] In our study group, the most frequent MEFV mutation was also M694V, and based on this result, we suggested that the distribution of MEFV gene mutations does not differ greatly between the different geographic areas of Turkey.…”

“…14 (Black Sea region/Turkey), Paa et al 13 (Southeastern region/Turkey) and Solak et al 4 (Aegean region/Turkey) reported that amyloidosis was more frequent in adult patients with the M694V/M694V genotype. Gürkan et al 5 (Trakya region/Turkey) also detected no amyloidosis in two adult patients with the M694V/ M694V genotype.…”