The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey

ERDOĞAN, Yalçıner; durmaz, zeynep hülya; Güçkan, Rıdvan; Celep, Gökçe; AKPINAR, Seviye; KAYA, Saban Abdullah

The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey

Gökçe CELEP, (Sabuncuoğlu Şerefeddin Eğitim ve Araştırma Hastanesi)

Zeynep Hülya DURMAZ, (Amasya Üniversitesi)

Yalçıner ERDOĞAN, (Amasya Üniversitesi)

Seviye AKPINAR, (Sabuncuoğlu Şerefeddin Eğitim ve Araştırma Hastanesi)

Saban Abdullah KAYA, (Sabuncuoğlu Şerefeddin Eğitim ve Araştırma Hastanesi)

Rıdvan GÜÇKAN (Amasya Üniversitesi)

Eurasian Journal of Medicine

2 0

Yıl: 2019 Cilt: 51 Sayı: 3 Sayfa Aralığı: 252 - 256 Metin Dili: İngilizce İndeks Tarihi: 24-04-2020

The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey

Öz:

Objective: Familial Mediterranean fever (FMF) is a common, inherited, autosomal recessive inflammatory disease in children. The diagnosis of FMF is based on clinical features and positive family history supported with genetic testing. This study aimed to determine the frequency and distribution of Mediterranean fever (MEFV) gene alterations of a city in Northern Anatolia.Materials and Methods: We evaluated MEFV gene mutations in 374 children preliminary diagnosed as FMF by a commercial kit based on real-time polymerase chain reaction technique in a one-year period, and screened 12 mutations.Results: At least one mutation was detected in 213 patients (57%) and 38 genotypes with 11 distinct mutations.A total of 137 (64. 3%) of mutation-positive children were heterozygous, 45 (21. 1%) were compound heterozygous, and 2 (0.9%) were complex heterozygous; and 14 (6.4%) patients were homozygous, 6 (2.8%) were compound homozygous, and 3 (1.4%) were complex homozygous. With a frequency of 50.1%, R202Q was the most common mutation. Also, R202Q/M694V was the most common compound heterozygous genotype. In 43 alleles, R202Q-M694V mutations were found to be in linkage disequilibrium. In our cohort, M694V, E148Q, V726A, and M680I (G/C) were other common mutations; whereas F479L, A744S, K695R, P369S, M694I, and R761H were the rare mutations. None of our patients had M680I (G/A) mutation.Conclusion: We determined the most common MEFV alteration prevalence in children of our region for the first time. The high R202Q mutation and linkage disequilibrium (LD) rates were the remarkable results of this study.

Anahtar Kelime:

Konular: Genel ve Dahili Tıp

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Shohat M. Familial Mediterranean fever. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mefford HC, Stephens K, Amemiya A, Ledbetter N (eds). GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; updated 2016 Dec 15.
2. Aydın F, Özçakar ZB, Yalçınkaya F. Familial Mediterranean fever: Diagnosis and treatment in children. Turkiye Klinikleri J Rheumatol-Special Topics 2017; 10: 46-54
3. Consortium FF. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31. [CrossRef]
4. Manukyan G, Rustam A. Update on Pyrin functions and mechanisms of Familial Mediterrenean Fever. Front Microbiol 2016; 7: 456. [CrossRef]
5. Yilmaz E, Ozen S, Balcı B, et al. Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 2001; 9: 553-5. [CrossRef]
6. Touitou, I., ed. (http://fmf.igh.cnrs.fr/infevers). 2017. Infevers: an evolving mutation database for autoinflammatory syndromes.
7. Yalçınkaya F, Ozen S, OzcakarZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology 2009; 48: 395-8. [CrossRef]
8. Turkish FMF Study Group. Familial Mediterranean fever (FMF) in Turkey Results of a Nationwide Multicenter Study. Medicine 2005;84: 1-11. [CrossRef]
9. Sayin Kocakap DB, Gunel-Ozcan, A, Cabuk, 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: 1419-26. [CrossRef]
10. Ritis K, Giaglis S, Spathari N, et al. Non-isotopic RNAase 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: 438-43. [CrossRef]
11. Giaglis S, Papadopoulos V, Kambas K, et al. MEFV alterations and population genetics analysis in a large cohort of Greek patients with familial Mediterranean fever. Clin Genet 2007; 71: 458-67. [CrossRef]
12. Özturk A, Ozcakar B, Ekim M, Akar N. Is MEFV gene Arg202Gln (605G > A) A disease-causing mutation? Turk J Med Sci 2008; 38: 205-8.
13. Yigit S, Karakus N, Tasliyurt T, Kaya SU, Bozkurt N, Kisacik B. Significance of MEFV gene R202Q polymorphismin Turkish familial Mediterranean fever patients. Gene 2012; 506: 43-5. [CrossRef]
14. Çomak E, Akman S, Koyun M, et al. Clinical evaluation of R202Q alteration of MEFV genes in Turkish children. Clin Rheumatol 2014; 33: 1765- 71. [CrossRef]
15. 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; 546: 195-9. [CrossRef]
16. Barut K, Şahin S, Adroviç A, Sinoplu AB, Yücel G, Pamuk G. Familial Mediterranean fever in childhood: a single center experience. RheumatolInt 2018; 38: 67-74. [CrossRef]
17. Coşkun S, Ustyol L, Bayram Y, et al. 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: 128-31. [CrossRef]
18. Kılınç M, Ganiyusufoglu E, Sager H, et al. 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. [CrossRef]
19. Ece A, Çakmak E, Uluca Ü, et al. The MEFV mutations and their clinical correlations in children with familial Mediterranean fever in southeast Turkey. Rheumatol Int 2014; 34: 207-12. [CrossRef]
20. Evliyaoglu O, Bilici S, Yolbas I, Kelekci S, Sen V. Common MEFV gene mutations in children with FMF in Diyarbakır, Turkey. Dicle Tıp Dergisi (Dicle Medical Journal) 2009; 36: 80-4. [CrossRef]
21. Majeed H, El-Khateeb M, El-Shanti H, Abu Rabaiha Z, Tayeh M, Najib D. The Spectrum of Familial Mediterranean Fever Gene Mutations in Arabs: Report of a Large Series. Semin Arthritis Rheum 2005; 34: 813-8. [CrossRef]
22. Sahin S, Ozyurt H, Akbas A, et al. Frequently seen mutations in MEFV gene in the FMF diseases in Tokat Region. Turk Klinik Biyokimya Derg (Journal of Turkish Clinical Biochemistry) 2009; 7: 81-6.
23. Gunel-Ozcan A, Sayin DB, Misirlioğlu ED, Güliter S, Yakaryilmaz F, Ensari C. The spectrum of FMF mutations and genotypes in the referrals to molecular genetics laboratory at Kirikkale University in Turkey. Mol Biol Rep 2009; 36: 757-60. [CrossRef]
24. 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: 1185-94. [CrossRef]
25. 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: 5065-69. [CrossRef]
26. Özalkaya E, Mir S, Sozeri B, Berdeli A, Mutlubas F, Cura A. Familial Mediterranean Fever gene mutation frequencies and genotype-phenotype correlations in the Aegean region of Turkey. Rheumatol Int 2011; 31: 779-84. [CrossRef]
27. Battal F, Silan F, Topaloğlu N, et al. The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population. Balkan J Med Genet 2017; 19: 23-8. [CrossRef]
28. Dogan H, Faruk Bayrak O, et al. Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations. Gene 2015; 568: 170-5. [CrossRef]
29. Öztuzcu S, Ulaşlı M, Ergun S, et al. Screening of common and novel familial mediterranean fever mutations in south-east part of Turkey. Mol Biol Rep 2014; 41: 2601-7. [CrossRef]
30. Barut K, Pamuk G, Adroviç A, et al. Comparison of Familial Mediterranean Fever and juvenile idiopathic arthritis patients according to family origin. Turk Pediatri Ars 2018; 53: 31-6. [CrossRef]

APA	Celep G, durmaz z, ERDOĞAN Y, AKPINAR S, KAYA S, Güçkan R (2019). The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. , 252 - 256.
Chicago	Celep Gökçe,durmaz zeynep hülya,ERDOĞAN Yalçıner,AKPINAR Seviye,KAYA Saban Abdullah,Güçkan Rıdvan The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. (2019): 252 - 256.
MLA	Celep Gökçe,durmaz zeynep hülya,ERDOĞAN Yalçıner,AKPINAR Seviye,KAYA Saban Abdullah,Güçkan Rıdvan The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. , 2019, ss.252 - 256.
AMA	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. . 2019; 252 - 256.
Vancouver	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. . 2019; 252 - 256.
IEEE	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R "The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey." , ss.252 - 256, 2019.
ISNAD	Celep, Gökçe vd. "The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey". (2019), 252-256.

APA	Celep G, durmaz z, ERDOĞAN Y, AKPINAR S, KAYA S, Güçkan R (2019). The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. Eurasian Journal of Medicine, 51(3), 252 - 256.
Chicago	Celep Gökçe,durmaz zeynep hülya,ERDOĞAN Yalçıner,AKPINAR Seviye,KAYA Saban Abdullah,Güçkan Rıdvan The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. Eurasian Journal of Medicine 51, no.3 (2019): 252 - 256.
MLA	Celep Gökçe,durmaz zeynep hülya,ERDOĞAN Yalçıner,AKPINAR Seviye,KAYA Saban Abdullah,Güçkan Rıdvan The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. Eurasian Journal of Medicine, vol.51, no.3, 2019, ss.252 - 256.
AMA	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. Eurasian Journal of Medicine. 2019; 51(3): 252 - 256.
Vancouver	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey. Eurasian Journal of Medicine. 2019; 51(3): 252 - 256.
IEEE	Celep G,durmaz z,ERDOĞAN Y,AKPINAR S,KAYA S,Güçkan R "The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey." Eurasian Journal of Medicine, 51, ss.252 - 256, 2019.
ISNAD	Celep, Gökçe vd. "The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey". Eurasian Journal of Medicine 51/3 (2019), 252-256.