Distribution of MEFV Gene Mutations and Allele Frequencies in Patients with Familial Mediterranean Fever - One Center Experience
Öz
FMF is an autosomal
recessive disorder affecting ethnic groups which is living in the
Mediterranean. The pyrin protein encoded by the MEFV gene, which leads to FMF,
is thought to play a negative regulatory role in the anti-inflammatory
response.
MEFV gene mutations
are thought to be responsible for most FMF patients. In this study, it was
aimed to determine the possible mutations in the MEFV gene of 5836 patients
with diagnosis of FMF and to evaluate the distribution of detected mutations
among Turkish FMF cases.
A 7-year patient
retrospective study with diagnosis of FMF was performed. Of the DNA samples
obtained from the cases, 22 mutations known to be related to disease in the
MEVF gene by pyrosequencing were studied.
In 5836 cases, 2774
(47,5%) mutations were detected and mutations which are related to examined
regions were not detected in 3062
(52,46%). In the study group, M694V(18,59%), E148Q (12,15%), V726A
(7,4%), M680I (G>C)(3,56 %), M680I
(G>A)(2,59 %), R761H (1,85 %), P369S (1,9 %)
and K695R (1,25 %) mutations were determined in 5836 cases.
In the findings
obtained in this study, types of MEFV gene mutation and frequencies in the
Turkish population were clearly shown in a large series of patients. We suggest
that these data could help to use more specific markers for the new FMF panels
for the Turkish community.
Anahtar Kelimeler
Kaynakça
- REFERANSLAR1. Ozen S, Batu ED, editors. The myths we believed in familial Mediterranean fever: what have we learned in the past years? Seminars in immunopathology; 2015: Springer.
- 2. Sarı İ, Birlik M, Kasifoğlu T. Familial Mediterranean fever: an updated review. European journal of rheumatology. 2014;1(1):21.
- 3. Daniels M, Shohat T, Brenner‐Ullman A, Shohat M. Familial Mediterranean fever: High gene frequency among the non‐Ashkenazic and ashkenazic Jewish populations in Israel. American Journal of Medical Genetics Part A. 1995;55(3):311-4.
- 4. Bakkaloglu A. Familial mediterranean fever. Pediatric Nephrology. 2003;18(9):853-9.
- 5. Group TFS. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine. 2005;84(1):1-11.
- 6. Yalçınkaya F, Cakar N, Mısırlıoğlu M, Tümer N, Akar N, Tekin M, et al. Genotype–phenotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation-independent amyloidosis. Rheumatology. 2000;39(1):67-72.
- 7. Örün E, Yalçınkaya F. TÜRK TIBBINDA AİLEVİ AKDENİZ ATEŞİ HASTALIĞI VE AMİLOİDOZ. 2003.
- 8. Alghamdi M. Familial Mediterranean fever, review of the literature. Clinical rheumatology. 2017;36(8):1707-13.
- 9. Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: current perspectives. Journal of inflammation research. 2016;9:13.
- 10. Abuhandan M, Kaya C, Güzelçiçek A. Ailevi Akdeniz ateşi tanısı alan 186 olgunun klinik semptom ve MEFV geni mutasyonlarının incelenmesi. Dicle Tıp Dergisi. 2015;42(1).
- 11. Tekin M, Yalçınkaya F, Tümer N, Cakar N, Kocak H. Familial Mediterranean fever and acute rheumatic fever: a pathogenetic relationship? Clinical rheumatology. 1999;18(6):446-9.
- 12. Zadeh N, Getzug T, Grody WW. Diagnosis and management of familial Mediterranean fever: integrating medical genetics in a dedicated interdisciplinary clinic. Genetics in medicine. 2011;13(3):263.
- 13. Papadopoulos V, Giaglis S, Mitroulis I, Ritis K. The Population Genetics of Familial Mediterranean Fever: A Meta‐Analysis Study. Annals of human genetics. 2008;72(6):752-61.
- 14. Dundar M, Emirogullari EF, Kiraz A, Taheri S, Baskol M. Common Familial Mediterranean Fever gene mutations in a Turkish cohort. Molecular biology reports. 2011;38(8):5065-9.
- 15. Yilmaz G, Senes M, Kayalp D, Yucel D. Is Turkish MEFV Mutations Spectrum Different Among Regions? Journal of clinical laboratory analysis. 2016;30(5):641-4.16. Giaglis S, Papadopoulos V, Kambas K, Doumas M, Tsironidou V, Rafail S, et al. MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Clinical genetics. 2007;71(5):458-67.
- 17. Solak M, Yıldız H, Köken R, Erdogan M, Eser B, Şen T, et al. Analysis of familial Mediterranean fever gene mutations in 202 patients with familial Mediterranean fever. Genetic testing. 2008;12(3):341-4.
- 18. Evliyaoglu O, Bilici S, Yolbas I, Kelekçi S, Sen V. Diyarbakır yöresi Ailevi Akdeniz Atesli çocuklarda MEFV gen mutasyon sıklıkları. Dicle Tıp Dergisi. 2009;36(2).
- 19. Coşku 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. Journal of genetics. 2015;94(4):629-35.
- 20. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F. MEFV mutations in patients with Familial Mediterranean Fever from the Aegean region of Turkey. Molecular biology reports. 2010;37(1):93-8.
- 21. Marek‐Yagel D, Berkun Y, Padeh S, Abu A, Reznik‐Wolf H, Livneh A, et al. Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis & Rheumatology. 2009;60(6):1862-6.
- 22. Olgun A, Akman S, Kurt I, Tuzun A, Kutluay T. MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis. Rheumatology international. 2005;25(4):255-9.
Ailesel Akdeniz Ateşi Tanısı Alan Olgularda MEFV Geni Mutasyonlarının ve Allel Frekanslarının Dağılımı - Tek Merkez Deneyimi
Öz
FMF sıklıkla
Akdeniz çevresinde yaşayan etnik grupları etkileyen, otozomal resesif geçişli
bir hastalıktır. FMF’e yol açan MEFV geninin kodladığı Pirin proteinin
antiinflamatuar yanıtta negatif bir düzenleyici olarak rol oynadığı
düşünülmektedir.
FMF hastalarının
çoğundan MEFV gen mutasyonlarının sorumlu olduğu düşünülmektedir. Bu çalışmada,
FMF tanısı almış 5836 olgunun MEFV genindeki olası mutasyonlarının tespit
edilmesi ve tespit edilen mutasyonların Türk FMF olguları arasındaki
dağılımının değerlendirilmesi amaçlanmıştır.
FMF tanısı almış, 7
yıllık hasta profili ile retrospektif bir çalışma yapılmıştır. Olgulardan elde
edilen DNA örneklerinden, pirosekanslama ile MEFV geninde hastalıkla ilişkisi
olduğu bilinen 22 mutasyon bölgesi çalışılmıştır. Toplam 5836 olgunun 2774’ünde
(% 47,5) mutasyon saptanırken, 3062’sinde (% 52,46) incelenen bölgelere ilişkin
mutasyon gözlenmemiştir. .Çalışma grubundaki 5836 olgunun % 18,59’de M694V, %
12,15’de E148Q, % 7,4’de V726A, % 3,56’de M680I (G>C), % 2,59’de M680I
(G>A), %1,85’de R761H, % 1,9’de P369S ve %1,25’de K695R mutasyonları tespit
edilmiştir.
Bu çalışmada elde
edilen bulgular doğrultusunda, Türk toplumundaki MEFV gen mutasyon tipleri ve
frekansları geniş bir hasta serisiyle net bir şekilde ortaya konulmuştur. Bu
verilerin Türk toplumunda yeni FMF panelleri için daha spesifik belirteçlerin
kullanılmasına yardımcı olabileceğini düşünmekteyiz.
Anahtar Kelimeler
Kaynakça
- REFERANSLAR1. Ozen S, Batu ED, editors. The myths we believed in familial Mediterranean fever: what have we learned in the past years? Seminars in immunopathology; 2015: Springer.
- 2. Sarı İ, Birlik M, Kasifoğlu T. Familial Mediterranean fever: an updated review. European journal of rheumatology. 2014;1(1):21.
- 3. Daniels M, Shohat T, Brenner‐Ullman A, Shohat M. Familial Mediterranean fever: High gene frequency among the non‐Ashkenazic and ashkenazic Jewish populations in Israel. American Journal of Medical Genetics Part A. 1995;55(3):311-4.
- 4. Bakkaloglu A. Familial mediterranean fever. Pediatric Nephrology. 2003;18(9):853-9.
- 5. Group TFS. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine. 2005;84(1):1-11.
- 6. Yalçınkaya F, Cakar N, Mısırlıoğlu M, Tümer N, Akar N, Tekin M, et al. Genotype–phenotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation-independent amyloidosis. Rheumatology. 2000;39(1):67-72.
- 7. Örün E, Yalçınkaya F. TÜRK TIBBINDA AİLEVİ AKDENİZ ATEŞİ HASTALIĞI VE AMİLOİDOZ. 2003.
- 8. Alghamdi M. Familial Mediterranean fever, review of the literature. Clinical rheumatology. 2017;36(8):1707-13.
- 9. Sönmez HE, Batu ED, Özen S. Familial Mediterranean fever: current perspectives. Journal of inflammation research. 2016;9:13.
- 10. Abuhandan M, Kaya C, Güzelçiçek A. Ailevi Akdeniz ateşi tanısı alan 186 olgunun klinik semptom ve MEFV geni mutasyonlarının incelenmesi. Dicle Tıp Dergisi. 2015;42(1).
- 11. Tekin M, Yalçınkaya F, Tümer N, Cakar N, Kocak H. Familial Mediterranean fever and acute rheumatic fever: a pathogenetic relationship? Clinical rheumatology. 1999;18(6):446-9.
- 12. Zadeh N, Getzug T, Grody WW. Diagnosis and management of familial Mediterranean fever: integrating medical genetics in a dedicated interdisciplinary clinic. Genetics in medicine. 2011;13(3):263.
- 13. Papadopoulos V, Giaglis S, Mitroulis I, Ritis K. The Population Genetics of Familial Mediterranean Fever: A Meta‐Analysis Study. Annals of human genetics. 2008;72(6):752-61.
- 14. Dundar M, Emirogullari EF, Kiraz A, Taheri S, Baskol M. Common Familial Mediterranean Fever gene mutations in a Turkish cohort. Molecular biology reports. 2011;38(8):5065-9.
- 15. Yilmaz G, Senes M, Kayalp D, Yucel D. Is Turkish MEFV Mutations Spectrum Different Among Regions? Journal of clinical laboratory analysis. 2016;30(5):641-4.16. Giaglis S, Papadopoulos V, Kambas K, Doumas M, Tsironidou V, Rafail S, et al. MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Clinical genetics. 2007;71(5):458-67.
- 17. Solak M, Yıldız H, Köken R, Erdogan M, Eser B, Şen T, et al. Analysis of familial Mediterranean fever gene mutations in 202 patients with familial Mediterranean fever. Genetic testing. 2008;12(3):341-4.
- 18. Evliyaoglu O, Bilici S, Yolbas I, Kelekçi S, Sen V. Diyarbakır yöresi Ailevi Akdeniz Atesli çocuklarda MEFV gen mutasyon sıklıkları. Dicle Tıp Dergisi. 2009;36(2).
- 19. Coşku 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. Journal of genetics. 2015;94(4):629-35.
- 20. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F. MEFV mutations in patients with Familial Mediterranean Fever from the Aegean region of Turkey. Molecular biology reports. 2010;37(1):93-8.
- 21. Marek‐Yagel D, Berkun Y, Padeh S, Abu A, Reznik‐Wolf H, Livneh A, et al. Clinical disease among patients heterozygous for familial Mediterranean fever. Arthritis & Rheumatology. 2009;60(6):1862-6.
- 22. Olgun A, Akman S, Kurt I, Tuzun A, Kutluay T. MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis. Rheumatology international. 2005;25(4):255-9.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | ORİJİNAL MAKALELER / ORIGINAL ARTICLES |
| Yazarlar | |
| Yayımlanma Tarihi | 12 Mart 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 40 Sayı: 2 |