The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia

Background/aim: The distribution of Mediterranean fever (MEFV) gene mutations in Turkish familial Mediterranean fever (FMF)patients varies according to geographic area of Turkey. There is a need for highly representative data for Turkish FMF patients. The aimof our study was to investigate the distribution of the common MEFV mutations in Turkish FMF patients in a nationwide, multicenterstudy.Materials and methods: Data of the 2246 FMF patients, from 15 adult rheumatology clinics located in different parts of the country,were evaluated retrospectively. The following mutations have been tested in all patients: M694V, M680I, M694I, V726A, and E148Q.Results: There were 1719 FMF patients with available genetic testing. According to the genotyping, homozygous M694V, present in413 patients (24%), was the most common mutation . One hundred and fifty-four (9%) of patients had no detectable mutations. Allelefrequencies of common mutations were: M694V (n = 1529, 44.5%), M680I (n = 423, 12.3%), V726A (n = 315, 9.2%), E148Q (n = 214,1%), and M694I (n = 12,

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1. Sari I, Birlik M, Kasifoglu T. Familial Mediterranean fever: an updated review. Eur J Rheumatol 2014; 1: 21-23.
2. Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, Saatci U, Bakkaloglu A, Ozguc M. Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 2001; 9: 553-555.
3. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yilmaz E et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 2005; 84: 1-11.
4. Ben-Zvi I, Herskovizh C, Kukuy O, Kassel Y, Grossman C, Livneh A. Familial Mediterranean fever without MEFV mutations: a case-control study. Orphanet Journal of Rare Diseases 2015; 10: 34.
5. http://fmf.igh.cnrs.fr/ISSAID/infevers/index.php
6. Kasifoglu T, Bilge SY, Sari I, Solmaz D, Senel S, Emmungil H, Kilic L, Oner SY, Yildiz F, Yilmaz S et al. Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study. Rheumatology (Oxford) 2014; 53: 741-745.
7. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, Migdal A, Padeh S, Pras M. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997; 40: 1879-1885.
8. Pras M. Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene. Scand J Rheumatol 1998; 27: 92-97.
9. Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, Pras M, Shinar Y. Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 2005; 64: 1009-1014.
10. Kisacik B, Yildirim B, Tasliyurt T, Ozyurt H, Ozyurt B, Yuce S, Kaya S, Ertenli I, Kiraz S. Increased frequency of familial Mediterranean fever in northern Turkey: a population-based study. Rheumatol Int 2009; 29: 1307-1309.
11. Touitou I. The spectrum of Familial Mediterranean fever (FMF) mutations. Eur J Hum Genet 2001; 9: 473-483.
12. Dundar M, Emirogullari EF, Kiraz A, Taheri S, Baskol M. Common familial Mediterranean fever gene mutations in a Turkish cohort. Mol Biol Rep 2011; 38: 5065-5069.
13. Akar N, Misiroglu M, Yalcinkaya F, Akar E, Cakar N, Tümer N, Akcakus M, Tastan H, Matzner Y. MEFV mutations in Turkish patients suffering from Familial Mediterranean Fever Hum Mutat. 2000; 15: 118-119.
14. Ceylan GG, Ceylan C, Ozturk E. Frequency of alterations in the MEFV gene and clinical signs in familial Mediterranean fever in Central Anatolia, Turkey. Genet Mol Res 2012; 11: 1185- 1194.
15. Demirkaya E, Tunca Y, Gok F, Ozen S, Gul D. A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish familial Mediterranean fever patients. Clin Rheumatol 2008; 27: 729-7232.
16. Oztuzcu S, Ulaşlı M, Ergun S, Iğci YZ, Iğci M, Bayraktar R, Nacarkahya G, Tamer A, Cevik MO, Cakmak EA et al. Screening of common and novel familial Mediterranean fever mutations in south-east part of Turkey. Mol Biol Rep 2014; 41: 2601-2607.
17. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F. MEFV mutations in patients with familial Mediterranean fever from the Aegean region of Turkey. Mol Biol Rep 2010; 37: 93-98.
18. Coşkun S, Kurtgöz S, Keskin E, Sönmez F, Bozkurt G. Frequency of mutations in Mediterranean fever gene, with gender and genotype-phenotype correlations in a Turkish population. J Genet 2015; 94: 629-635.
19. Dogan H, Faruk Bayrak O, Emet M, Keles M, Gulluoglu S, Gul Z, Pirim I. Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations. Gene 2015; 568: 170-175.
20. Coşkun S, Ustyol L, Bayram Y, Selçuk Bektaş M, Gulsen S, Çim A, Uluca U, Savaş D. The spectrum of MEFV gene mutations and genotypes in Van province, the eastern region of Turkey, and report of a novel mutation (R361T). Gene 2015; 562: 128-131.
21. Etem EO, Deveci SD, Erol D, Yuce H, Elyas H. Familial Mediterranean Fever: a retrospective clinical and molecular study in the East of Anatolia region of Turkey. Open Rheumatol J 2010; 4: 1-6.
22. Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, Aydın AK, Dasdemir S, Turanlı ET, Buyru N et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 2018; 38: 67-74.
23. Kilinc M, Ganiyusufoglu E, Sager H, Celik A, Olgar S, Cetin GY, Davutoglu M, Altunoren.O. The report of sequence analysis on familial Mediterranean fever gene (MEFV) in South-eastern Mediterranean region (Kahramanmaraş) of Turkey. Rheumatol Int 2016; 36: 25-31.
24. Sayın Kocakap DB, Günel-Özcan A, Çabuk F, Ensari C. The frequency of familial Mediterranean fever gene mutations and genotypes at Kirikkale and comparison with the mean of regional MEFV mutation frequency of Turkey. Mol Biol Rep 2014; 41: 1419-1426.
25. Gunesacar R, Celik MM, Arica V, Elmacioglu S, Ozturk OH . Frequency of MEFV gene mutations in Hatay province, Mediterranean region of Turkey and report of a novel missense mutation (I247V). Gene 2014:10; 546: 195-199.
26. Ece A, Çakmak E, Uluca Ü, Kelekçi S, Yolbaş İ, Güneş A, Yel S, Tan İ, Şen V. The MEFV mutations and their clinical correlations in children with familial Mediterranean fever in southeast Turkey. Rheumatol Int 2014; 34: 207-212.
27. Lidar M, Tokov I, Chetrit A, Zaks N, Langevitz P, Livneh A. Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps disclosed. Clin Exp Rheumatol 2005; 23: 357-363.
28. Marek-Yagel D, Berkun Y, Padeh S, Abu A, Reznik-Wolf H, Livneh A, Pras M, Pras E. Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis Rheum 2009; 60: 1862-1866.
29. Booty MG, Chae JJ, Masters SL, Remmers EF, Barham B, Le JM, Barron KS, Holland SM, Kastner DL, Aksentijevich I. Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 2009; 60: 1851-1861.
30. Evliyaoglu O, Bilici S, Yolbaş I, Kelekci S, Sen V. Diyarbakır yöresi Ailevi Akdeniz Atesli çocuklarda MEFV gen mutasyon sıklıkları. Dicle Tıp Dergisi 2009: 36; 80-84 (article in Turkish).