Skip to main content
SpringerLink
Log in

Common Familial Mediterranean Fever gene mutations in a Turkish cohort

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder with the responsible gene of MEFV which primarily affects Jewish, Armenian, Turkish and Arab populations. The FMF gene (MEFV) has recently been cloned to chromosome 16p, which encodes pyrin. In the present study, we enrolled 2,067 unrelated patients with the suspicion of FMF in Middle Anatolia between the years 2006–2009 and identified the 12 MEFV mutations. DNA was amplified by PCR and subjected to reverse hybridization for the detection of MEFV gene mutations. Among the 2,067 patients, 866 (41.9%) were males and 1,201 (58.1%) were females. The mutations were homozygous in 176 (16.85%) patients, compound heterozygous in 314 (30.1%) patients, heterozygous in 546 (52.25%) patients and the other forms of mutations were found in 8 patients (0.76%). No mutation was detected in 1,023 (49.5%) patients. The most frequent mutations were M694V, M680I (G/C), E148Q and V726A. We could not find any significant differences between the two common mutations according to the gender. The high incidence of MEFV gene mutations in the Turkish population indicated that newborn screening may be discussed in the future. Because of the ethnic origin of Anatolia, larger serial analyses are necessary to investigate the rate and coexistence of these mutations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bonyadi M, Esmaeili M, Jalali H, Somi MH, Ghaffari A, Rafeey M, Sakha K, Lotfalizadeh N, Pourhassan A, Khoshbaten M, Ardalan MR, Laghaeian N (2009) MEFV mutations in Iranian Azeri Turkish patients with Familial Mediterranean Fever. Clin Genet Nov 76(5):477–480

    Article  CAS  Google Scholar 

  2. Koca S, Etem E, Isik B, Yuce H, Ozgen M, Dag MS, Isik A (2010) Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid arthritis. Joint Bone Spine 77(1):32–35

    Article  PubMed  CAS  Google Scholar 

  3. Lidar M, Livneh A (2007) Familial Mediterranean Fever: clinical, molecular and management advancements. Neth J Med 65:318–324

    PubMed  CAS  Google Scholar 

  4. Drenth JP, Van der Meer JW (2001) Hereditary periodic fever. N Engl J Med 345:1748–1757

    Article  PubMed  CAS  Google Scholar 

  5. Booth DR, Gillmore JD, Lachmann HJ (2000) The genetic basis of autosomal dominant Familial Mediterranean Fever. Q J Math 93:217–221

    CAS  Google Scholar 

  6. Saatçi U, Ozen S, Ozdemir S, Bakkaloglu A, Besbas N, Topaloglu R, Arslan S (1997) Familial Mediterranean Fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis. Eur J Pediatr 156:619–623

    Article  PubMed  Google Scholar 

  7. Sohar E, Gafni J, Pras M, Heller H (1967) Familial Mediterranean Fever. A survey of 470 cases and review of the literature. Am J Med 43:227–253

    Article  PubMed  CAS  Google Scholar 

  8. Simon A, Van der Meer JW (2007) Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am J Physiol Regul Integr Comp Physiol 292:R86–R98

    Article  PubMed  CAS  Google Scholar 

  9. Eisenberg S, Aksentijevich I, Deng Z, Kastner DL, Matzner Y (1998) Diagnosis of Familial Mediterranean Fever by a molecular genetics method. Ann Intern Med 129:539–542

    PubMed  CAS  Google Scholar 

  10. Dode C, Pecheux C, Cazeneuve C, Cattan D, Dervichian M, Goossens M, Delpech M, Amselem S, Grateau G (2000) Mutations in the MEFV gene in a large series of patients with a clinical diagnosis of Familial Mediterranean Fever. Am J Med Genet 92(4):241–246

    Article  PubMed  CAS  Google Scholar 

  11. Livneh A, Langevitz P, Zemer D, Padeh S, Migdal A, Sohar E, Pras M (1997) Criteria for the diagnosis of Familial Mediterranean Fever. Arthritis Rheum 40:1879–1885

    Article  PubMed  CAS  Google Scholar 

  12. Pasa S, Altintas A, Devecioglu B, Cil T, Danis R, Isi H, Bayan K, Tuzun Y, Ecer S, Batun S, Ayyildiz O (2008) Familial Mediterranean Fever gene mutations in the southeastern region of Turkey and their phenotypical features. Amyloid 15(1):49–53

    Article  PubMed  CAS  Google Scholar 

  13. Yilmaz E, Ozen S, Balci B, Duzova A, Topaloglu R, Besbas N, Saatci U, Bakkaloglu A, Ozguc M (2001) Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9:553–555

    Article  PubMed  CAS  Google Scholar 

  14. Jarjour RA (2010) Familial Mediterranean Fever in Syrian patients: MEFV gene mutations and genotype–phenotype correlation. Mol Biol Rep 37(1):1–5

    Article  PubMed  CAS  Google Scholar 

  15. Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yilmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E, Turkish FMF Study Group (2005) Familial Mediterranean Fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 84:1–11

    Article  PubMed  Google Scholar 

  16. Samli H, Dogru O, Bukulmez A, Yuksel E, Ovali F, Solak M (2006) Relationship of Tel Hashomer criteria and Mediterranean fever gene mutations in a cohort of Turkish Familial Mediterranean Fever patients. Saudi Med J 27:1822–1826

    PubMed  Google Scholar 

  17. Ertekin V, Selimoglu MA, Pirim I (2005) Familial Mediterranean Fever in a childhood population in eastern Turkey. Pediatr Int 47:640–644

    Article  PubMed  Google Scholar 

  18. Ozcan A, Sayin DB, Misirlioglu ED, Güliter S, Yakaryilmaz F, Ensari C (2009) The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at Kirikkale University in Turkey. Mol Biol Rep 36(4):757–760

    Article  Google Scholar 

  19. Touitou I (2001) The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet 9:473–483

    Article  PubMed  CAS  Google Scholar 

  20. Demirkaya E, Tunca Y, Gok F, Ozen S, Gul D (2008) A very frequent mutation and remarkable association of R761H with M694V mutations in Turkish FMF patients. Clin Rheumatol 27:729–732

    Article  PubMed  Google Scholar 

  21. Ureten K, Gonulalan G, Akbal E, Güneş F, Akyürek O, Ozbek M, Oztürk MA (2009) Demographic, clinical and mutational characteristics of Turkish Familial Mediterranean Fever patients: results of a single center in central Anatolia. Rheumatol Int 29(12):1477–1480

    Article  PubMed  Google Scholar 

  22. Yepiskoposyan L, Harutyunyan A (2007) Population genetics of Familial Mediterranean Fever: a review. Eur J Hum Genet 15:911–916

    Article  PubMed  CAS  Google Scholar 

  23. Sabbagh AS, Ghasham M, Abdel Khalek R, Greije L, Shammaa DM, Zaatari GS, Mahfouz RA (2008) MEFV gene mutations spectrum among Lebanese patients referred for Familial Mediterranean Fever work-up: experience of a major tertiary care center. Mol Biol Rep 35:447–451

    Article  PubMed  CAS  Google Scholar 

  24. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F (2010) MEFV mutations in patients with Familial Mediterranean Fever from the Aegean region of Turkey. Mol Biol Rep 37(1):93–98

    Article  PubMed  CAS  Google Scholar 

  25. El-Garf A, Salah S, Iskander I, Salah H, Amin SN (2010) MEFV mutations in Egyptian patients suffering from Familial Mediterranean Fever: analysis of 12 gene mutations. Rheumatol Int 30(10):1293–1298

    Article  PubMed  CAS  Google Scholar 

  26. Yesilada E, Savaci S, Yüksel S et al (2005) MEFV mutations in cases with Familial Mediterranean Fever (FMF). İnönü Üniversitesi Tıp Fakültesi Dergisi 12(4):235–238

    Google Scholar 

  27. Sarkisian T, Ajrapetian H, Beglarian A, Shahsuvarian G, Egiazarian A (2008) Familial Mediterranean Fever in Armenian population. Georgian Med News 156:105–111

    PubMed  Google Scholar 

  28. Rogers DB, Shohat M, Petersen GM, Bickal J, Congleton J, Schwabe AD, Rotter JI (1989) Familial Mediterranean Fever in Armenians: autosomal recessive inheritance with high gene frequency. Am J Med Genet 34:168–172

    Article  PubMed  CAS  Google Scholar 

  29. Rawashdeh MO, Majeed HA (1996) Familial Mediterranean Fever in Arab children: the high prevalence and gene frequency. Eur J Pediatr 155:540–544

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Gökmen Zararsiz for the statistical analysis of this study.

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Erciyes University Medicine Faculty Kayseri, 38039, Kayseri, Turkey

    Munis Dundar, Elif Funda Emirogullari, Aslihan Kiraz & Serpil Taheri

  2. Department of Internal Medicine, Erciyes University Medicine Faculty Kayseri, Kayseri, Turkey

    Mevlut Baskol

Authors
  1. Munis Dundar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elif Funda Emirogullari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aslihan Kiraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Serpil Taheri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mevlut Baskol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Munis Dundar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dundar, M., Emirogullari, E.F., Kiraz, A. et al. Common Familial Mediterranean Fever gene mutations in a Turkish cohort. Mol Biol Rep 38, 5065–5069 (2011). https://doi.org/10.1007/s11033-010-0652-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-010-0652-7

Keywords

Search

Navigation