Fonksiyonel karın ağrısı olan çocuklarda MEFV genlerinin artan sıklığı

Yıl 2020, Cilt: 20 Sayı: 3, 157 - 161, 11.01.2022

Erkan Doğan Eylem Sevinç Burcu Korkut Emre Taşkın Nergiz Sevinç

https://doi.org/10.17941/agd.1055302

Öz

Giriş ve Amaç: Fonksiyonel karın ağrısı olan çocuklarda MEFV gen mutasyonlarının sıklığını araştırmak. Gereç ve Yöntem: Kesitsel tipteki bu çalışma, Karabük Üniversitesi Tıp Fakültesi, Pediatri ve Pediatrik Gastroenteroloji Bilim Dalı’nda Ocak 2020-Aralık 2020 tarihleri arasında fonksiyonel karın ağrısı olan 1135 çocuk üzerinde yapıldı. Ailevi Akdeniz ateşi gen mutasyon analizi için genomik mini kit (Macherey-Nagel, Almanya) kullanılarak periferik kan lökositlerinden DNA ekstrakte edildi. MEFV geninin tüm kodlama bölgeleri ve ekzon-intron birleşimindeki 25 baz çifti incelendi. Bulgular: Fonksiyonel karın ağrısı olan 1135 hastanın (525 kız, %46.2) ortalama yaşı 9.4 yıldı. Yüz otuz dokuz (%12.2) çocukta en az 1 MEFV mutasyonu veya polimorfizmi bulundu. En yaygın MEFV gen değişikliği heterozigot p.M694V- (%3.7) olup, bunu p.E148Q- (%2.1), p.M680I- (%1.1) ve p.V726A- (%1.05) mutasyonları izledi. Heterozigot 3 mutasyon (p.P369S, p.E148Q, p.M680I) sadece 1 (%0.08) çocukta tespit edildi. Sonuç: Bu çalışma, fonksiyonel karın ağrısı olan çocuklarda MEFV gen mutasyonlarının bulunabileceğini göstermektedir. MEFV gen mutasyonlarının fonksiyonel karın ağrısında rol oynayıp oynamayacağına dair fazla ve kapsamlı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler

Fonksiyonel karın ağrısı, MEFV, çocuk

Increased frequency of MEFV genes in children with functional abdominal pain

Öz

Background and Aims: To investigate the frequency of MEFV gene mutations in children with functional abdominal pain. Materials and Methods: The cross sectional study was conducted in 1135 children diagnosed with functional abdominal pain at the Departments of Pediatric and Pediatric Gastroenterology of Karabük University Medical Faculty in Karabük, Turkey, from January 2020 to December 2020. For familial Mediterranean fever gene mutation analysis, genomic DNA was extracted from peripheral blood leukocytes using the mini kit (Macherey-Nagel, Germany). All coding regions of the MEFV gene and 25 base pairs in the exon-intron junction were examined. Results: The median age of 1135 patients with functional abdominal pain (525 female, 46.2%) were 9.4 years. One hundred thirty-nine (12.2%) children were found at least 1 MEFV mutation or polymorphism. The most common MEFV gene alteration was heterozygous p.M694V- (3.7%), followed by p.E148Q- (2.1%), p.M680I- (1.1%) and p.V726A- (%1.05). Heterozygous 3 mutations (p.P369S, p.E148Q, p.M680I) were detected in only 1 (0.08%) child. Conclusion: Present study indicates that MEFV gene mutations could be found among children with functional abdominal pain. Further and comprehensive studies are required whether MEFV gene mutations may play a role in the functional abdominal pain or not.

Anahtar Kelimeler

Functional abdominal pain, MEFV, child

Kaynakça

• 1. Padeh S, Berkun Y. Auto-inflammatory fever syndromes. Rheum Dis Clin North Am 2007;33:585-623
• 2. French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31.
• 3. Ozen S, Karaaslan Y, Ozdemir O, et al. Prevalence of juvenile chronic arthritis and familial Mediterranean fever in Turkey: a field study. J Rheumatol 1998;25:2445-9.
• 4. Ong FS, Vakil H, Xue Y, et al. The M694V mutation in Armenian-Americans: a 10-year retrospective study of MEFV mutation testing for familial Mediterranean fever at UCLA. Clin Genet 2013;84:55-9.
• 5. Ben-Chetrit E, Levy M. Familial Mediterranean Fever. Lancet 1998;351:659-64.
• 6. Campbell L, Raheem I, Malemud CJ, Askari AD. The relationship between NALP3 and autoinflammatory syndromes. Int J Mol Sci 2016;17:725.
• 7. Zeevenhooven J, Koppen IJ, Benninga MA. The new Rome IV criteria for functional gastrointestinal disorders in infants and toddlers. Pediatr Gastroenterol Hepatol Nutr 2017;20:1-13.
• 8. Akar HH, Yıldız M, Sevinc E, Sokucu S. The influence of HLA-DQ2 heterodimers on the clinical features and laboratory of patients with celiac disease. Nutr Hosp 2015;32:2594-9.
• 9. Koppen IJ, Nurko S, Saps M, Di Lorenzo C, Benninga MA. The pediatric Rome IV criteria: what's new? Expert Rev Gastroenterol Hepatol 2017;11:193-201.
• 10. Brusaferro A, Farinelli E, Zenzeri L, Cozzali R, Esposito S. The management of paediatric functional abdominal pain disorders: latest evidence. Pediatr Drugs 2018;20:235-47.
• 11. Fikree A, Byrne P. Management of functional gastrointestinal disorders. Clin Med (Lond) 2021;21:44-52.
• 12. Coskun BD, Kiraz A, Sevinc E, Baspınar O, Cakmak E. Increased frequency of MEFV genes in patients with epigastric pain syndrome. Balkan J Med Genet 2017;20:51-8.
• 13. Börekci E, Celikbilek M, Soytürk M, et al. Functional gastrointestinal disorders in patients with familial Mediterranean fever. Int J Rheum Dis 2017;20:2101-5.
• 14. Ekinci RMK, Balcı S, Akay E, et al. Frequency of functional gastrointestinal disorders in children with familial Mediterranean fever. Clin Rheumatol 2019;38:921-6.
• 15. Güncan S, Bilge NŞ, Cansu DÜ, Kaşifoğlu T, Korkmaz C. The role of MEFV mutations in the concurrent disorders observed in patients with familial Mediterranean fever. Eur J Rheumatol 2016;3:118-21.
• 16. Ozdogan H, Arisoy N, Kasapcapur O, et al. Vasculitis in familial Mediterranean fever. J Rheumatol 1997;24:323-7.
• 17. Comak E, Dogan CS, Akman S, et al. MEFV gene mutations in Turkish children with juvenile idiopathic arthritis. Eur J Pediatr 2013;172:1061-7.
• 18. Cakici EK, Kurt Şükür ED, Özlü SG, et al. MEFV gene mutations in children with Henoch–Schönlein purpura and their correlations-do mutations matter? Clin Rheumatol 2019;38:1947-52.
• 19. Urganci N, Ozgenc F, Kuloglu Z, et al; Turkish IBD Study Group. Familial Mediterranean fever mutation analysis in pediatric patients with inflammatory bowel disease: A multicenter study. Turkish J Gastroenterol 2021;32:248-61.
• 20. Erdogan H, Sonkur AC, Görükmez O, et al. The frequency of familial Mediterranean fever gene mutations and the correlations between phenotype and genotype in Turkish children. Asian Journal of Pediatric Research 2020;4:20-6.