Evaluation of the frequency of MEFV gene variants in patients with a pre-diagnosis of Familial Mediterranean Fever (FMF) in southeast Türkiye

Öz

Purpose: Familial Mediterranean Fever (FMF) is a hereditary auto inflammatory disease (MIM#249100). The most common symptoms are abdominal pain, high fever, and arthralgia. FMF is the result of variants in the MEditerraneanFeVer (MEFV) gene located on chromosome 16p13.3, which contains 10 exons and encodes the pyrin (marenostrin) protein. The frequency of MEFV gene variants that cause FMF varies according to ethnic groups, countries and even different regions in the same country. In our study, we aimed to determine the frequency and distribution of MEFV gene changes that cause Familial Mediterranean fever in southeast Türkiye. Materials and methods: A total of 6.660 patients with a pre-diagnosis of FMF, including 3.495 women and 3.165 men, were included in the study. Fragment analysis was performed to investigate the MEFV gene variants of the patients and the 19 most common variants in the Turkish population were examined. Results: We found at least one variant in 50.17% (3.341) of our 6.660 patients. In our patients, 108 different genotypes; in Exon 2, 3, 5 and 10 and we identified 16 different variants. We found 2.120 (63.21%) patients were heterozygous, 693 (20.74%) were compound heterozygotes, 275 (8.23%) were homozygous and 261 (7.81%) were complex genotypes. The five variants with the highest allele frequency are; R202Q (27.84%), M694V (22.83%), E148Q (21.98%), V726A (7.42%), and M680I (G>C) (6.39%). Conclusion: We identified the most common prevalence of MEFV gene alteration in a large patient group in our region. High R202Q mutation rates were among the remarkable results of this study.

Anahtar Kelimeler

• FMF
• MEFV gene variations
• fragment analysis

Türkiye'nin güneydoğusunda Ailevi Akdeniz Ateşi (AAA) ön tanısı alan hastalardaki MEFV gen varyantlarının sıklığının değerlendirilmesi

Öz

Amaç: Ailevi Akdeniz Ateşi (AAA) kalıtsal bir otoinflamatuar hastalıktır (MIM#249100). En sık görülen semptomlar yüksek ateş, karın ağrısı ve artraljidir. AAA, 16p13.3 kromozomu üzerinde yer alan, 10 ekzondan oluşan ve pirin (marenostrin) proteinini kodlayan MEditerraneanFeVer (MEFV) genindeki varyantların sonucudur. AAA'ya neden olan MEFV gen varyantlarının sıklığı etnik gruplara, ülkelere ve hatta aynı ülke içindeki farklı bölgelere göre değişmektedir. Bu çalışmada, Türkiye'nin güneydoğusunda Ailesel Akdeniz ateşine neden olan MEFV gen değişikliklerinin sıklığını ve dağılımını belirlemeyi amaçladık. Gereç ve yöntem: Çalışmaya Ailevi Akdeniz Ateşi ön tanısı almış olan 3,495 kadın ve 3,165 erkek olmak üzere toplam 6.660 hasta dahil edildi. Hastaların MEFV gen varyantlarını araştırmak için fragman analizi yapıldı ve Türk popülasyonunda en sık görülen 19 varyant incelendi. Bulgular: Çalışmaya dahil edilen 6,660 hastamızın %50,17'sinde (3,341) en az bir varyant tespit edildi. Hastalarımızda 108 farklı genotip; Exon 2, 3, 5 ve 10'da olmak üzere 16 farklı varyant belirledik. Hastaların 2,120’sinde (%63,21) heterozigot, 693’ünde (%20,74) bileşik heterozigot, 275’inde (%8,23) homozigot ve 261’inde (%7,81) kompleks genotip bulundu. Alel frekansı en yüksek olan 5 varyant sırasıyla; R202Q (%27,84), M694V (%22,83), E148Q (%21,98), V726A (%7,42) ve M680I (G>C) (%6,39) olarak belirlendi. Sonuç: Bölgemizde geniş bir hasta grubunda yaptığımız bu çalışma ile FMF ön tanısı almış olan hastalarda en sık görülen MEFV gen değişikliklerinin sıklığını ve dağılımını belirledik. Yüksek R202Q mutasyon oranları bu çalışmanın dikkat çekici sonuçları arasında yer almaktadır.

Anahtar Kelimeler

• FMF
• MEFV gen varyasyonları
• fragman analizi

Kaynakça

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