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Ailevi Akdeniz Ateşi Hastalarında Gen Mutasyonlarının Hastalık Ciddiyet Skorları Üzerine Etkisi

Yıl 2022, Cilt: 32 Sayı: 1, 19 - 26, 28.02.2022
https://doi.org/10.54005/geneltip.1002843

Öz

Amaç: Ailevi Akdeniz Ateşi (AAA) kendi kendini sınırlayan otoinflamatuar bir hastalıktır. Hastalıkların prognozunu daha iyi anlamak için çeşitli klinik kriterlerin bir kombinasyonuna göre puanlanan hastalık şiddeti skorları kullanılır. Bu çalışmanın amacı, AAA’lı çocuklarda genetik mutasyonların hastalık şiddeti skorlarına etkisini belirlemektir.
Gereç ve Yöntemler: Yalçınkaya-Özen tanı kriterlerine göre FMF tanısı konan ve gen analizi yapılan 0-18 yaş arası 303 hasta retrospektif olarak değerlendirildi. Tüm hastalara Pras ve arkadaşlarının skorlama sistemi, Mor ve arkadaşlarının skorlama sistemi ve Uluslararası FMF şiddet skoru (ISSF) skorlama sistemi uygulandı. Genotipler hastalık şiddeti skorlarına göre karşılaştırıldı.
Bulgular: Hastalar Pras ve ark. skoruna göre M694V homozigot, heterozigot, M694V/diğer allel kombine heterozigot ve diğer mutasyonlar olarak 4 gruba ayrıldığında M694V homozigot grubunda hafif hastalık sıklığı daha az olma eğilimindeydi. Pras ve ark.'nın skoruna göre hastalar homozigot M694V, heterozigot M694V, heterozigot E148Q ve heterozigot M694V/M680I kombine mutasyonlar olarak ayrıldığında, homozigot M694V grubunda hafif hastalık daha az yaygın olarak bulundu. Hastalar homozigot M694V grubu ve heterozigot M694V grubu olarak ikiye ayrıldığında, üç skorlama sistemine göre homozigot M694V grubunda hastalık daha şiddetliydi.
Sonuçlar: Pras ve ark. tarafından tanımlanan skorlama sistemine göre, homozigot M694V alleli olan hastalarda şiddetli hastalık oranı, homozigot grupla karşılaştırıldığında heterozigot grupta istatistiksel olarak anlamlı derecede daha yüksekti.

Kaynakça

  • REFERENCES 1. Ozen S, Bilginer Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol. 2014; 10(3):135-47.
  • 2. Yalçınkaya F, Group TFS. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. 2005.
  • 3. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007; 65(9): 318-24.
  • 4. Cobankara V. Kiraz S. Ailesel akdeniz ateşi Hacettepe Tıp Dergisi Hacettepe Üniversitesi yayınları Ankara. 2000; 31: 310-9.
  • 5. Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020;50(SI-2): 1591-610.
  • 6. Consortium FF. A candidate gene for familial Mediterranean fever. Nature genetics. 1997; 17(1): 25-31.
  • 7. Schnappauf O, Chae JJ, Kastner DL, Aksentijevich I. The Pyrin Inflammasome in Health and Disease. Front Immunol. 2019; 10: 1745.
  • 8. Pras E, Livneh A, Balow Jr JE, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. American journal of medical genetics. 1998; 75(2): 216-9.
  • 9. Mor A, Shinar Y, Zaks N, et al., editors. Evaluation of disease severity in familial Mediterranean fever. Seminars in arthritis and rheumatism; 2005: Elsevier.
  • 10. Demirkaya E, Acikel C, Hashkes P, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Annals of the Rheumatic Diseases. 2016; 75(6): 1051-6.
  • 11. Yalçınkaya F, Özen S, Özçakar ZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology. 2009; 48(4): 395-8.
  • 12. Gattorno M, Hofer M, Federici S, et al. Classification criteria for autoinflammatory recurrent fevers. Annals of the rheumatic diseases. 2019;78(8): 1025-32.
  • 13. 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 journal of medical genetics: BJMG. 2016; 19(2): 23.
  • 14. Wilson M, Abou-Elalla AA, Zakaria MT,et al. Serum amyloid A Type 1 gene polymorphism in Egyptian children with familial Mediterranean fever. Pathobiology. 2016; 83(6): 295-300.
  • 15. Yavuz S, Duru NS, Elevli M. Ailevi Akdeniz Ateşi Hastalarında Klinik, Laboratuvar Bulguları, Hastalık Ağırlık Skorları ve Gen Mutasyonları Arasındaki İlişki. Medical Bulletin of Haseki/Haseki Tip Bulteni. 2018; 56(1).
  • 16. Yalçınkaya F, Cakar N, Mısırlıoğlu 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.
  • 17. Soylemezoglu O, Kandur Y, Duzova A, et al. Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort. Clinical and experimental rheumatology. 2015; 33(6 Suppl 94): 152-5.
  • 18. Aydın F, Çakar N, Özçakar ZB, et al. Clinical features and disease severity of Turkish FMF children carrying E148Q mutation. J Clin Lab Anal. 2019; 33(4): e22852.
  • 19. Ayaz NA, Tanatar A, Karadag SG, et al. Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever. Rheumatol Int. 2021; 41(1): 113-20.
  • 20. Guler T, Garip Y, Dortbas F, Dogan YP. Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue, psychological status, disease severity and other clinical parameters. The Egyptian Rheumatologist. 2018; 40(2): 117-21.

The Effect of Gene Mutations on Disease Severity Scores in Pediatric Familial Mediterranean Fever Patients

Yıl 2022, Cilt: 32 Sayı: 1, 19 - 26, 28.02.2022
https://doi.org/10.54005/geneltip.1002843

Öz

Objectives: Familial Mediterranean Fever (FMF) is a self-limiting autoinflammatory disease. In order to better understand the prognosis of diseases, disease severity scores are used. The aim of this study is to determine the effect of genetic mutations on disease severity scores in children with FMF.
Methods: 303 patients between the ages of 0-18, who were diagnosed with FMF according to Yalçınkaya-Özen diagnostic criteria and whose gene analysis was studied, were evaluated retrospectively. Pras et al's scoring system, Mor et al's scoring system and International severity score of FMF (ISSF) scoring system were applied to all patients. Genotypes were compared according to disease severity scores.
Results: When the patients were divided into 4 groups as M694V homozygous, heterozygous, M694V/other allele combined heterozygous and other mutations, according to the score of Pras et al., the frequency of mild disease tended to be less in the M694V homozygous group. When the patients divided as homozygous M694V, heterozygous M694V, heterozygous E148Q, heterozygous M694V/M680I combined mutations, according to the score of Pras et al., mild disease was found to be less common in the homozygous M694V group. When patients were divided into homozygous and heterozygous M694V groups, the disease was more severe in the homozygous M694V group according to the three scoring systems.
Conclusions: Based on the scoring system described by Pras et al., the rate of severe disease was higher in patients with homozygous M694V allele, whereas the rate of mild disease was statistically significantly higher in the heterozygous group compared with homozygous group.

Kaynakça

  • REFERENCES 1. Ozen S, Bilginer Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat Rev Rheumatol. 2014; 10(3):135-47.
  • 2. Yalçınkaya F, Group TFS. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. 2005.
  • 3. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Neth J Med. 2007; 65(9): 318-24.
  • 4. Cobankara V. Kiraz S. Ailesel akdeniz ateşi Hacettepe Tıp Dergisi Hacettepe Üniversitesi yayınları Ankara. 2000; 31: 310-9.
  • 5. Tufan A, Lachmann HJ. Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020;50(SI-2): 1591-610.
  • 6. Consortium FF. A candidate gene for familial Mediterranean fever. Nature genetics. 1997; 17(1): 25-31.
  • 7. Schnappauf O, Chae JJ, Kastner DL, Aksentijevich I. The Pyrin Inflammasome in Health and Disease. Front Immunol. 2019; 10: 1745.
  • 8. Pras E, Livneh A, Balow Jr JE, et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. American journal of medical genetics. 1998; 75(2): 216-9.
  • 9. Mor A, Shinar Y, Zaks N, et al., editors. Evaluation of disease severity in familial Mediterranean fever. Seminars in arthritis and rheumatism; 2005: Elsevier.
  • 10. Demirkaya E, Acikel C, Hashkes P, et al. Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF). Annals of the Rheumatic Diseases. 2016; 75(6): 1051-6.
  • 11. Yalçınkaya F, Özen S, Özçakar ZB, et al. A new set of criteria for the diagnosis of familial Mediterranean fever in childhood. Rheumatology. 2009; 48(4): 395-8.
  • 12. Gattorno M, Hofer M, Federici S, et al. Classification criteria for autoinflammatory recurrent fevers. Annals of the rheumatic diseases. 2019;78(8): 1025-32.
  • 13. 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 journal of medical genetics: BJMG. 2016; 19(2): 23.
  • 14. Wilson M, Abou-Elalla AA, Zakaria MT,et al. Serum amyloid A Type 1 gene polymorphism in Egyptian children with familial Mediterranean fever. Pathobiology. 2016; 83(6): 295-300.
  • 15. Yavuz S, Duru NS, Elevli M. Ailevi Akdeniz Ateşi Hastalarında Klinik, Laboratuvar Bulguları, Hastalık Ağırlık Skorları ve Gen Mutasyonları Arasındaki İlişki. Medical Bulletin of Haseki/Haseki Tip Bulteni. 2018; 56(1).
  • 16. Yalçınkaya F, Cakar N, Mısırlıoğlu 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.
  • 17. Soylemezoglu O, Kandur Y, Duzova A, et al. Familial Mediterranean fever with a single MEFV mutation: comparison of rare and common mutations in a Turkish paediatric cohort. Clinical and experimental rheumatology. 2015; 33(6 Suppl 94): 152-5.
  • 18. Aydın F, Çakar N, Özçakar ZB, et al. Clinical features and disease severity of Turkish FMF children carrying E148Q mutation. J Clin Lab Anal. 2019; 33(4): e22852.
  • 19. Ayaz NA, Tanatar A, Karadag SG, et al. Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever. Rheumatol Int. 2021; 41(1): 113-20.
  • 20. Guler T, Garip Y, Dortbas F, Dogan YP. Quality of life in Turkish patients with Familial Mediterranean Fever: Association with fatigue, psychological status, disease severity and other clinical parameters. The Egyptian Rheumatologist. 2018; 40(2): 117-21.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Original Article
Yazarlar

Vildan Güngörer 0000-0002-9838-2603

Alaaddin Yorulmaz 0000-0001-5478-1197

Şükrü  Arslan 0000-0001-5632-8273

Yayımlanma Tarihi 28 Şubat 2022
Gönderilme Tarihi 1 Ekim 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 32 Sayı: 1

Kaynak Göster

Vancouver Güngörer V, Yorulmaz A, Arslan Ş. The Effect of Gene Mutations on Disease Severity Scores in Pediatric Familial Mediterranean Fever Patients. Genel Tıp Derg. 2022;32(1):19-26.