The aim of this study was to determine the Mediterranean fever (MEFV) gene mutations and their clinical correlations in children with familial Mediterranean fever (FMF) in southeast Turkey. Clinical and laboratory characteristics of 147 (65 males, 82 females) consecutive children with FMF having a positive MEFV gene mutation were prospectively investigated. Patients with negative MEFV gene mutations or atypical FMF presentations and those from other regions of the country were excluded. Clinical manifestations and disease severity scores were recorded. The six most frequent MEFV mutations including M694V, V726A, R726H, P369S, E148Q and P369S were investigated by a reverse hybridization test method. The median age of study group was 9.0 years, median age at diagnosis was 7.8 years, median age at disease onset was 5.0 years, and median follow-up duration was 4.0 years. A positive family history of FMF and parent-to-offspring transmission was found in 58.5 and 42.2 % of families, respectively. The frequencies of independent alleles, with decreasing order, were E148Q (30.7 %), M694V (26.0 %), R761H (13.5 %), V726A (13.0 %), P369S (10.5 %) and M680I (6.3 %) in FMF patients. The M694V subgroup had higher mean disease severity score and longer attack duration compared with E148Q and other mutations subgroups (p < 0.05). Two patients with amyloidosis had the M694V homozygote genotype. In conclusion contrast to other regions and many other ethnicities of the world, the most frequent MEFV gene mutation was E148Q in southeast Turkey. The M694V mutation frequency was lower, and disease severity was relatively mild in FMF children of this region.
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Ben-Chetrit E, Touitou I (2012) The impact of MEFV gene identification on FMF: an appraisal after 15 years. Clin Exp Rheumatol 30:S3–S6PubMedGoogle Scholar
Berkun Y, Eisenstein E, Ben-Chetrit E (2012) FMF—clinical features, new treatments and the role of genetic modifiers: a critical digest of the 2010–2012 literature. Clin Exp Rheumatol 30:S90–S95PubMedGoogle Scholar
Tunca M, Akar S, Onen F et al (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 84:1–11CrossRefGoogle Scholar
Brik R, Shinawi M, Kepten I et al (1999) Familial Mediterranean fever: clinical and genetic characterization in a mixed pediatric population of Jewish and Arab Patients. Pediatrics 103:e70–e70PubMedCrossRefGoogle Scholar
Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T (2009) Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis 68:246–248. doi:10.1136/ard.2008.092031PubMedCrossRefGoogle Scholar
Ozen S, Demirkaya E, Amaryan G, et al. (2013) Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children. Ann Rheum Dis. doi:10.1136/annrheumdis-2012-202708
Yalçınkaya F, Çakar N, Mısırlıoğlu M et al (2000) Genotype–phenotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation-independent amyloidosis. Rheumatology 39:67–72. doi:10.1093/rheumatology/39.1.67PubMedCrossRefGoogle Scholar
Ozturk C, Halicioglu O, Coker I et al (2012) Association of clinical and genetical features in FMF with focus on MEFV strip assay sensitivity in 452 children from western Anatolia, Turkey. Clin Rheumatol 31:493–501. doi:10.1007/s10067-011-1876-1PubMedCrossRefGoogle Scholar
Touitou I, Sarkisian T, Medlej-Hashim M et al (2007) Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. International Study Group for Phenotype-Genotype Correlation in familial Mediterranean fever. Arthritis Rheum 56:1706–1712PubMedCrossRefGoogle Scholar
Onen F, Sumer H, Turkay S et al (2004) Increased frequency of familial Mediterranean fever in Central Anatolia, Turkey. Clin Exp Rheumatol 22:S31–S33PubMedGoogle Scholar