The effects of R202Q genotype on the clinical features of familial mediterranean fever: single center experiences

Year 2021, Volume: 14 Issue: 4, 870 - 877, 01.10.2021

Serkan Türkuçar Hatice Adıgüzel Ceren Yılmaz Erbil Ünsal

https://doi.org/10.31362/patd.885049

Abstract

R202Q gen değişikliğinin ailesel akdeniz ateşi kliniği üzerine etkisi: tek merkez deneyimi

Abstract

Amaç: Ailesel Akdeniz ateşinin kliniğinde görülen tekrarlayan febril poliserozit atakları, MEFV genindeki mutasyonlara bağlı kontrolsüz interlökin 1-β salınımından kaynaklanmaktadır ve hastalığın seyri mutasyonlara göre değişkenlik gösterebilmektedir. Bu çalışmada R202Q gen değişiminin klinik ve laboratuvar bulguları üzerindeki etkisinin değerlendirmesi amaçlanmıştır.
Gereç ve yöntem: 122 pediatrik AAA hastasının demografik, klinik ve laboratuvar verileri kıyaslanmıştır. Hastalar MEFV mutasyonlarına göre R202Q değişimini heterozigot, homozigot, ekzon-10 mutasyonları ile bileşik heterozigot bulunduranlar ve sadece ekzon-10 mutasyonu bulunduranlar olarak gruplandırılarak karşılaştırılmıştır.
Bulgular: Demografik, antropometrik, klinik ve laboratuvar bulgular açısından değerlendirildiğinde, gruplar arasında herhangi bir istatistiksel anlamlı fark saptanmamıştır.
Sonuç: R202Q gen değişikliğine sahip hastalarda da ekzon 10 mutasyonlu hastalar gibi tipik AAA klinik bulguları gözlenebilmektedir. Ailesel Akdeniz ateşi, genotipik ve fenotipik özelliklerinin birlikte değerlendirilmesi gereken bir hastalıktır.

Keywords

MEFV mutasyonu, Ekzon-2, Ailesel Akdeniz Ateşi, R202Q

References

• 1. Özen S. Update on the epidemiology and disease outcome of Familial Mediterranean fever. Best Pract Res Clin Rheumatol 2018;32:254-260. https://doi.org/10.1016/j.berh.2018.09.003
• 2. Özen S, Batu ED, Demir S. Familial Mediterranean Fever: recent developments in pathogenesis and new recommendations for management. Front Immunol 2017;8:253. https://doi.org/10.3389/fimmu.2017.00253
• 3. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell 1997;90:797-807. https://doi.org/10.1016/s0092-8674(00)80539-5
• 4. French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31. https://doi.org/10.1038/ng0997-25
• 5. Infevers genetical database. Available at: https:// https://infevers.umai-montpellier.fr/web/search.php?n=1. Accessed Jan 14, 2021
• 6. Yaşar Bilge Ş, Sarı İ, Solmaz D, et al. The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia. Turk J Med Sci 2019;49:472-477. https://doi.org/10.3906/sag-1809-100
• 7. Celep G, Durmaz ZH, Erdogan Y, Akpinar S, Kaya SA, Guckan R. The Spectrum of MEFV gene mutations and genotypes in the Middle Northern Region of Turkey. Eurasian J Med, 2019;51:252-256. https://doi.org/10.5152/eurasianjmed.2019.18396
• 8. 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. https://doi.org/10.1007/s11033-009-9543-1 9. Akpolat T, Özkaya O, Özen S. Homozygous M694V as a risk factor for amyloidosis in Turkish FMF patients. Gene 2012;492:285-289. https://doi.org/10.1016/j.gene.2011.10.012
• 10. Lidar M, Yonath H, Shechter N, et al. Incomplete response to colchicine in M694V homozygote FMF patients. Autoimmun Rev, 2012;12:72-76. https://doi.org/10.1016/j.autrev.2012.07.025
• 11. Akpolat T, Yilmaz E, Ozen S, Akpolat I, Danaci M, Kandemir B. M680I(Arm2)/M694V(Med) mutations in a patient with familial Mediterranean fever and polyarteritis nodosa. Nephrol Dial Transplant, 1998;13:2633-2635. https://doi.org/10.1093/ndt/13.10.2633
• 12. Bernot A, da Silva C, Petit JL, et al. Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet 1998;7:1317-1325. https://doi.org/ 10.1093/hmg/7.8.1317
• 13. Ritis K, Giaglis S, Spathari N, et al. Non-isotopic RNase cleavage assay for mutation detection in MEFV, the gene responsible for familial Mediterranean fever, in a cohort of Greek patients. Ann Rheum Dis 2004:63:438-443. https://doi.org/10.1136/ard.2003.009258
• 14. Ozturk A, Ozcakar B, Ekim M, Akar N. Is MEFV gene Arg202Gln (605 G>A) A disease-causing mutation? Turk J Med Sci 2008;38:205-208.
• 15. Yigit S, Karakus N, Tasliyurt T, Uzun Kaya S, Bozkurt N, Kisacik B. Significance of MEFV gene R202Q polymorphismin Turkish familial Mediterranean fever patients. Gene 2012;506:43-45. https://doi.org/10.1016/j.gene.2012.06.074
• 16. Infevers genetical database. Available at: https:// https://infevers.umai-montpellier.fr/web/detail_mutation.php (Accessed Jan 14, 2021.)
• 17. Yalçinkaya F, Ozen S, Ozçakar ZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology (Oxford) 2009;48(4):395-398. https://doi.org/10.1093/rheumatology/ken509
• 18. Nevzi O, Günöz H, Furman A, et al. Türk çocuklarında vücut ağırlığı, boy uzunluğu, baş çevresi ve vücut kitle indeksi referans değerleri. Çocuk Sağlığı ve Hastalıkları Dergisi 2008;51:1-14.
• 19. Pras E, Livneh A, Jr Balow JE, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 1998;13;75(2):216-219. https://doi.org/10.1002/(sici)1096-8628(19980113)75:2<216::aid-jmg20>3.0.co;2-r
• 20. Sönmezgöz E, Özer S, Gül A, et al. Clinical and demographic evaluation according to MEFV genes in patients with familial mediterranean fever. Biochem Genet 2019;57:289-300. https://doi.org/ 10.1007/s10528-018-9889-y
• 21. Kirectepe AK, Kasapcopur O, Arisoy N, et al. Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever. BMC Med Genet 2011;12:105. https://doi.org/10.1186/1471-2350-12-105
• 22. Comak E, Akman S, Koyun M, et al. Clinical evaluation of R202Q alteration of MEFV genes in Turkish children. Clin Rheumatol 2014;33:1765-1771. https://doi.org/10.1007/s10067-014-2602-6
• 23. Milenković J, Vojinović J, Debeljak M, et al. Distribution of MEFV gene mutations and R202Q polymorphism in the Serbian population and their influence on oxidative stress and clinical manifestations of inflammation. Pediatr Rheumatol Online J 2016;14:39. https://doi.org/10.1186/s12969-016-0097-1
• 24. Bayram MT, Çankaya T, Bora E, et al. Risk factors for subclinical inflammation in children with Familial Mediterranean fever. Rheumatol Int 2015;35:1393-1398. https://doi.org/10.1007/s00296-015-3227-z
• 25. Özer S, Yılmaz R, Sönmezgöz E, et al. Simple markers for subclinical inflammation in patients with Familial Mediterranean Fever. Med Sci Monit 2015;21:298-303. https://doi.org/10.12659/MSM.892289
• 26. Balkarli A, Akyol M, Tepeli E, Elmas L, Cobankara V. MEFV gene variation R202Q is associated with metabolic syndrome. Eur Rev Med Pharmacol Sci 2016;20:3255-3261.
• 27. Fentoğlu Ö, Dinç G, Bağcı Ö, et al. R202Q/M694V as novel MEFV gene mutations in chronic periodontitis and familial Mediterranean fever. J Periodontal Res 2017;52:994-1003. https://doi.org/10.1111/jre.12467