Skip to main content
SpringerLink
Log in

MEFV mutations in patients with familial Mediterranean fever from the Aegean region of Turkey

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Familial Mediterranean Fever (FMF) which is frequently present in Mediterranean populations is caused by mutations in the MEFV gene. According to recent data, MEFV mutations are not the only cause of FMF, but these are major genetic determinants which cause FMF. It has also been suggested that there may be a number of other genes causing FMF. The MEFV gene is located at 16p13.3 and encodes a protein, pyrin/marenostrin. More than 70 disease associated mutations and totally 186 mutations and polymorphisms have been defined in affected individuals. We have retrospectively evaluated the molecular test results of 1,201 patients identified as having FMF clinical symptoms referred to the Molecular Genetics Laboratory of the Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir/Turkey over the last 4 years. Patients were tested for 12 common mutations in the MEFV gene using a strip assay method (Innogenetics, Belgium). Out of the 1,201 patients tested (2,402 chromosomes) in the Aegean region in Turkey, 654 (54.45%) did not carry any mutations, among the 547 (45.55%) patients with mutations 246 patients were either homozygous (101) or compound heterozygous (145), 296 carried only one detected mutation, and five patients had three mutations. Allelic frequencies for the four most common mutations in the mutation positive groups were 47.60% (M694V), 16.75% (E148Q), 12.95% (V726A), 11.94% (M680I G/C).The remaining alleles (10.76%) showed rare mutations which were R761H, P369S, A744S, K695R, F479L, M694I. When the frequencies of mutations detected in our group were compared to the frequencies reported in the other regions of Turkey, an increase in V726A mutation frequency was observed. No patient showed a I692del mutation which is sometimes evident in other Mediterranean populations.

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. The Turkish FMF Study Group (FMF-TR) (2005) Familial Mediterranean fever in Turkey: the results of a nationwide multicenter study. Medicine 84(1):1–11. doi:10.1097/01.md.0000152370.84628.0c

    Article  Google Scholar 

  2. Kogan A, Shinar Y, Lidar M et al (2001) Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotype III states and absence of perceptible biological advantage for the carrier state. Am J Med Genet 102:272–276. doi:10.1002/ajmg.1438

    Article  CAS  PubMed  Google Scholar 

  3. Rawashdeh MO, Majeed HA (1996) Familial Mediterranean fever in Arab children: the high prevalence and gene frequency. Eur J Pediatr 155:540–544. doi:10.1007/BF01957901

    Article  CAS  PubMed  Google Scholar 

  4. Ozen S (2003) Familial Mediterranean fever: revisiting an ancient disease. Eur J Pediatr 162(7-8):449–454

    Article  PubMed  Google Scholar 

  5. Delibaş A, Oner A, Balci B, Demircin G, Bulbul M, Bek K, Erdoğan O, Baysun S, Yilmaz E (2005) Genetic risk factors of amyloidogenesis in familial Mediterranean fever. Am J Nephrol 25(5):434–440

    Article  PubMed  CAS  Google Scholar 

  6. Atagunduz MP, Tuglular S, Kantarci G, Akoglu E, Direskeneli H (2004) Association of FMF-related (MEFV) point mutations with secondary and FMF amyloidosis. Nephron Clin Pract 96(4):c131–c135. doi:10.1159/000077375

    Article  CAS  PubMed  Google Scholar 

  7. Pras M, Bronshpigel N, Zemer D, Gafni J (1982) Variable incidence of amyloidosis in familial Mediterranean fever among different ethnic groups. Johns Hopkins Med J 150(1):22–26

    CAS  PubMed  Google Scholar 

  8. The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90(4):797–807

    Article  Google Scholar 

  9. The French FMF Consortium (1997) A candidate gene for familial Mediterranean fever. Nat Genet 17(1):25–31

    Article  Google Scholar 

  10. Topaloglu R, Ozaltin F, Yilmaz E, Ozen S, Balci B, Besbas N, Bakkaloglu A (2005) E148Q is a disease-causing MEFV mutation: a phenotypic evaluation in patients with familial Mediterranean fever. Ann Rheum Dis 64(5):750–752

    Article  CAS  PubMed  Google Scholar 

  11. Tchernitchko D, Legendre M, Cazeneuve C, Delahaye A, Niel F, Amselem S (2003) The E148Q MEFV allele is not implicated in the development of familial Mediterranean fever. Hum Mutat 22(4):339–340

    Article  PubMed  CAS  Google Scholar 

  12. Kotone-Miyahara Y, Takaori-Kondo A, Fukunaga K, Goto M, Hayashino Y, Miki M, Takayama H, Sasada M, Uchiyama T (2004) E148Q/M694I mutation in 3 Japanese patients with familial Mediterranean fever. Int J Hematol 79(3):235–237

    Article  CAS  PubMed  Google Scholar 

  13. Solak M, Yildiz H, Koken R, Erdogan M, Eser B, Sen T, Evirgen N, Erdem S, Arikan E (2008) Analysis of familial meditarrenean fever gene mutations in 202 patients with familial meditarrenean fever. Genet test 12(3):341–344

    Article  CAS  PubMed  Google Scholar 

  14. Gunel-Ozcan A, Sayın DB, Mısırlıoglu ED, Guliter S, Yakaryilmaz F, Ensari C (2008) The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at Kırıkkale University in Turkey. Mol Biol Rep. doı: 10.1007/s11033-008-9240-5

  15. 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  CAS  PubMed  Google Scholar 

  16. Yigit S, Bagci H, Ozkaya O, Ozdamar K, Cengiz K, Akpolat T (2008) MEFV mutations in patients with familial Mediterranean fever in Black Sea region of Turkey: Samsun experience. J Rheumatol 35(1):106–113

    PubMed  Google Scholar 

  17. Cakar N, Yalçinkaya F, Ozkaya N, Tekin M, Akar N, Koçak H, Misirlioğlu M, Akar E, Tümer N (2001) Familial Mediterranean fever (FMF)-associated amyloidosis in childhood. Clinical features, course and outcome. Clin Exp Rheumatol 19(5, 24):S63–S67

    CAS  PubMed  Google Scholar 

  18. Akar N, Misiroglu M, Yalcinkaya F et al (2000) MEFV mutations in Turkish patients suffering from familial Mediterranean fever. Hum Mutat 15(1):118–119. doi:10.1002/(SICI)1098-1004(200001)15:1<118::AID-HUMU29>3.0.CO;2-5

    Article  CAS  PubMed  Google Scholar 

  19. Ertekin V, Selimoğlu MA, Pirim I (2005) Familial Mediterranean fever in a childhood population in eastern Turkey. Pediatr Int 47(6):640–644

    Article  PubMed  Google Scholar 

  20. Tchernitchko D, Legendre M, Delahaye A, Cazeneuve C, Niel F, Goossens M, Amselem S, Girodon E (2003) Clinical evaluation of a reverse hybridization assay for the molecular detection of twelve MEFV gene mutations. Clin Chem 49(11):1942–1945

    Google Scholar 

  21. 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 familial Mediterranean fever patients. Clin Rheumatol 27(6):729–732

    Google Scholar 

  22. Toutiou I (2001) The spectrum of Familial Mediterranean Fever (FMF) mutations. Eur J Hum Genet 9:473–483. doi:10.1038/sj.ejhg.5200658

    Article  CAS  Google Scholar 

  23. Medlej-Hashim M, Serre JL, Corbani S, Saab O, Jalkh N, Delague V, Chouery E, Salem N, Loiselet J, Lefranc G, Mégarbané A (2005) Familial Mediterranean fever (FMF) in Lebanon and Jordan: a population genetics study and report of three novel mutations. Eur J Med Genet 48(4):412–420

    Article  PubMed  Google Scholar 

  24. El-Shanti H, Majeed HA, El-Khateeb M (2006) Familial Mediterranean fever in Arabs. Lancet 367(9515):1016–1024

    Article  PubMed  Google Scholar 

  25. Kir T, Güleç M, Bakir B, Hosgönül E, Tümerdem N (2005) The frequency and effecting factors of consanguineous marriage in a group of soldiers in Ankara. J Biosoc Sci 37(4):519–523

    Article  PubMed  Google Scholar 

  26. 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(3):447–451

    Google Scholar 

  27. 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(7):553–555

    Article  CAS  PubMed  Google Scholar 

  28. La Regina M, Nucera G, Diaco M, Procopio A, Gasbarrini G, Notarnicola C, Kone-Paut I, Touitou I, Manna R (2003) Familial Mediterranean fever is no longer a rare disease in Italy. Eur J Hum Genet 11:50–56. doi:10.1038/sj.ejhg.5200916

    Article  PubMed  Google Scholar 

  29. Aldea A, Calafell F, Arostegui JI, Lao O, Rius J, Plaza S, Mas’o M, Vives J, Buades J, Yag¨ue J (2004) The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination ‘‘hotspot’’ at the MEFV locus. Hum Mutat 23:399–406. doi:10.1002/humu.9229

    Article  PubMed  Google Scholar 

  30. Giaglis S, Papadopoulos V, Kambas K, Doumas M, Tsironidou V, Rafail S, Kartalis G, Speletas M, Ritis K (2007) MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Clin Genet 71:458–467. doi:10.1111/j.1399-0004.2007.00789.x

    Article  CAS  PubMed  Google Scholar 

  31. Papadopoulos VP, Giaglis S, Mitroulis I, Ritis K (2008) The Population Genetics of Familial Mediterranean Fever: A Meta-Analysis Study. Ann Hum Genet 72(6):752–761. doi:10.1111/j.1469-1809.2008.00471.x

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Faculty, Department of Medical Genetics, Ege University, Izmir, Turkey

    Haluk Akin, Huseyin Onay, Emre Turker, Ozgur Cogulu & Ferda Ozkinay

Authors
  1. Haluk Akin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huseyin Onay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emre Turker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ozgur Cogulu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ferda Ozkinay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haluk Akin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akin, H., Onay, H., Turker, E. et al. MEFV mutations in patients with familial Mediterranean fever from the Aegean region of Turkey. Mol Biol Rep 37, 93–98 (2010). https://doi.org/10.1007/s11033-009-9543-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-009-9543-1

Keywords

Search

Navigation