Research Article
BibTex RIS Cite

Clinical and Laboratory Reflection of Mutation Positivity at the Exon 10 Position in Patients with Familial Mediterranean Fever

Year 2024, Volume: 50 Issue: 1, 29 - 33, 17.05.2024

Tuğba Ocak Ahmet Görünen Burcu Yağız Belkıs Nihan Coşkun Şebnem Özemri Sağ Hüseyin Ediz Dalkılıç Yavuz Pehlivan

https://doi.org/10.32708/uutfd.1410535

Abstract

Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent episodes of fever and serositis due to mutations in the 10-exon Mediterranean Fever (MEFV) gene. Mutation positivity at the exon 10 site is associated with the typical clinical phenotype and disease complications such as amyloidosis and renal failure. In our study, we aimed to determine the relationship between the presence of a mutation in the 10th exon and the clinical features and complications. The files of 354 patients who were followed up in the rheumatology clinic of our hospital between January 2015 and August 2023 with a diagnosis of FMF were analyzed retrospectively. The patients were divided into two groups depending on the presence of a mutation in exon 10. Male sex ratio, abdominal pain, frequency of amyloidosis, creatinine, neutrophil and c-reactive protein levels in the attack-free period were significantly higher in the group with positive mutation in exon 10 (p=0.044, p=0.039, p<0.001, p=0.028, p=0.015, p=0.030, respectively). Clinical and laboratory features differ in patients with a positive mutation in exon 10, and close monitoring of these patients can reduce disease-related complications.

Keywords

Familial Mediterranean Fever Exon 10 Male gender Amyloidosis

References

  • 1. Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227-53. doi: 10.1016/0002-9343(67)90167-2
  • 2. Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Rheum 2009;61:1447-53. doi: 10.1002/art.24458
  • 3. The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90:797-807. doi: 10.1016/S0092-8674(00) 80539-5
  • 4. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol 2011;7:105-12. doi: 10.1038/nrrheum.2010.181
  • 5. French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31. doi: 10.1038/ng0997-25
  • 6. Gangemi S, Manti S, Procopio V, et al. Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: a systematic review. Clin Genet 2018;94:81-94. doi: 10.1111/cge.13223
  • 7. Ayaz NA, Tanatar A, Karadag SG, et al. Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever. Rheumatol Int 2021;41:113-20. doi: 10.1007/s00296-020-04592-7
  • 8. Ben-Chetnt E, Levy M. Familial Meditarrenan Fever. Lancet 1998;351:659-64. doi: 10.1016/S0140-6736(97)09408-7
  • 9. Ozen S, Batu ED. The myths we believed in familial Mediterranean fever: what have we learned in the past years? Semin Immuno pathol 2015;37:363-9. doi: 10.1007/s00281-015-0484-6
  • 10. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F. MEFV mutations in patients with Familial Mediterranean Fever from the Aegean region of Turkey. Mol Biol Rep 2010; 37:93-8. doi: 10.1007/s11033-009-9543-1
  • 11. Ben-Chetrit E, Yazici H. Familial Mediterranean fever: different faces around the world. Clin Exp Rheumatol 2019;121:18-22.
  • 12. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997;40:1879-85. doi: 10.1002/art.1780401023
  • 13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83. doi: 10.1016/0021-9681(87)90171-8
  • 14. Migita K, Agematsu K, Yazaki M, et al. Familial Mediterranean fever: genotypephenotype correlations in Japanese patients. Medicine 2014;93:158-64. doi: 10.1097/MD.0000000000000029
  • 15. Samuels J, Aksentıjevıch I, Torosyan Y, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine 1998;77:268-97. doi: 10.1097/00005792-199807000-00005
  • 16. Sari I, Birlik M, Kasifoglu T. Familial Mediterranean fever: an updated review. Eur J Rheumatol 2014;1:21-33. doi: 10.5152/eurjrheum.2014.006
  • 17. Yasar Bilge NS, Bodakcı E, Bilge U, Kasifoğlu T. Gender is not a Prognostic Factor for Familial Mediterranean Fever. Ankara Med J 2019;4:716-21. doi: 10.17098/amj.651961
  • 18. Tunca M, Akar S, Onen F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 2005;84:1-11. doi: 10.1097/01.md.0000152370.84628.0c
  • 19. Dewalle M, Domingo C, Rozenbaum M, et al. Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF). Eur J Hum Genet 1998;6: 95-7. doi: 10.1038/ sj.ejhg.5200170
  • 20.Kunt SS, Aydin F, Cakar N, Ozdel S, et al. The effect ofgenotype on musculoskeletal complaints in patients with familial Mediterranean fever. Postgrad Med 2020;132:220-4. doi: 10.1080/00325481.2019.1708147
  • 21.Özdel S, Özçakar ZB, Kunt SS, Elhan AH, Yalçinkaya F. Late-onset disease is associated with a mild phenotype in children with familial Mediterranean fever. Clin Rheumatol 2016;35:1837-40. doi: 10.1007/s10067-016-3196-y
  • 22.Barut K, Sahin S, Adrovic A, et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 2018;38:67-74. doi: 10.1007/s00296-017-3796-0
  • 23.Öztürk K, Çakan M. The analysis of genotype-phenotypecorrelation in familial Mediterranean fever. Pediatr Int2022;64:e15017. doi: 10.1111/ped.15017
  • 24.Öztürk K, Çakan M. Protracted febrile myalgia syndrome as the first manifestation of familial Mediterranean fever in children: case-based review. Rheumatol Int 2021; 41:213-8. doi: 10.1007/s00296-020-04696-0
  • 25.Hotta Y, Kawasaki T, Kotani T, et al. Familial Mediterranean fever without fever. Intern Med 2020; 59:1267-70. doi: 10.2169/internalmedicine.3175-19
  • 26.Blomqvist A, Engblom D. Neural mechanisms of inflammation-induced fever. Neuroscientist 2018;24:381-99. doi: 10.1177/1073858418760481
  • 27.Engström L, Ruud J, Eskilsson A, et al. Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells. Endocrinology 2012;153:4849–61. doi: 10.1210/en.2012-1375
  • 28.Öztürk K, Coşkuner T, Baglan, et al. Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort. Front Pediatr 2022;9:805919. doi: 10.3389/fped.2021.805919
  • 29.Mukhin NA, Kozlovskaya LV, Bogdanova MV et al. Predictors of AA amyloidosis in familial Mediterranean fever. Rheumatol Int 2015;35:1257-61. doi:10.1007/s00296-014-3205-x
  • 30.Yasar Bilge NS, Sari I, Solmaz D, et al. Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis 2018;21:880-4. doi: 10.1111/1756-185X.13259
  • 31.Sonmez HE, Esmeray P, Batu ED, et al. Is age associated with disease severity and compliance to treatment in children with familial Mediterranean fever? Rheumatol Int 2019;39:83-7. doi: 10.1007/s00296-018-4123-0
  • 32.Kasifoglu T, Bilge SY, Sari I et al. Amyloidosis and its relatedfactors in Turkish patients with familial Mediterranean fever: amulticentre study. Rheumatology (Oxford) 2014;53:741-5. doi: 10.1093/rheumatology/ket400
  • 33.Cazeneuve C, Ajrapetyan H, Papin S, et al. Identification ofMEFV-independent modifying genetic factors for familial Mediterranean fever. Am J Hum Genet 2000;67:1136-43. doi: 10.1016/S0002-9297(07)62944-9
  • 34.Gershoni‐Baruch R, Brik R, Zacks N, et al. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever.Arthritis Rheum 2003;48:1149-55. doi: 10.1002/art.10944
  • 35.Parmaksız G, Noyan ZA. Can RDW be used as a screening test for subclinical infammation in children with FMF? Is RDW related to MEFV gene mutations? Clin Rheumatol 2023;42:197-202. doi:10.1007/s10067-022-06358-x
  • 36.Van der Hilst JCH, Simon A, Drenth JPH. Hereditary periodicfever and reactive amyloidosis. Clin Exp Med 2005;5:87-98 doi: 10.1007/s10238-005-0071-6

Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması

Year 2024, Volume: 50 Issue: 1, 29 - 33, 17.05.2024

Tuğba Ocak Ahmet Görünen Burcu Yağız Belkıs Nihan Coşkun Şebnem Özemri Sağ Hüseyin Ediz Dalkılıç Yavuz Pehlivan

https://doi.org/10.32708/uutfd.1410535

Abstract

Ailevi Akdeniz Ateşi (AAA) 10 ekzondan oluşan Mediterranean Fever (MEFV) geninde meydana gelen mutasyonlar sonucu tekrarlayan ateş ve serözit ataklarıyla seyreden otoinflamatuar bir hastalıktır. Ekzon 10 lokasyonunda mutasyon pozitifliği tipik klinik fenotiple ve amiloidoz, böbrek yetmezliği gibi hastalık komplikasyonlarıyla ilişkilidir. Çalışmamızda 10. ekzonda mutasyon varlığının klinik özellikler ve komplikasyonlar ile ilişkisini saptamayı amaçladık. Hastanemiz romatoloji kliniğinde Ocak 2015-Ağustos 2023 tarihleri arasında AAA tanısı ile takip edilen 354 hastanın dosyası retrospektif olarak incelendi. Hastalar ekzon 10 lokasyonunda mutasyon bulunma durumuna göre iki gruba ayrıldı. Ekzon 10’da mutasyon pozitifliği olan grupta erkek cinsiyet oranı, karın ağrısı, amiloidoz görülme sıklığı, ataksız dönemdeki kreatinin, nötrofil ve c-reaktif protein değerleri anlamlı olarak daha yüksek saptandı (sırasıyla p=0,044, p=0,039, p<0.001, p=0,028, p=0,015, p=0,030). Ekzon 10 lokasyonunda mutasyon pozitifliği olan hastalarda klinik ve laboratuvar özellikler farklılık göstermekte olup, bu hastaların yakın takip edilmesi ile hastalıkla ilişkili kompikasyonlar azaltılabilir.

Keywords

Ailevi Akdeniz Ateşi Ekzon 10 Erkek cinsiyet Amiloidoz

References

  • 1. Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967;43:227-53. doi: 10.1016/0002-9343(67)90167-2
  • 2. Chetrit E, Touitou I. Familial Mediterranean fever in the world. Arthritis Rheum 2009;61:1447-53. doi: 10.1002/art.24458
  • 3. The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90:797-807. doi: 10.1016/S0092-8674(00) 80539-5
  • 4. Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol 2011;7:105-12. doi: 10.1038/nrrheum.2010.181
  • 5. French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997;17:25-31. doi: 10.1038/ng0997-25
  • 6. Gangemi S, Manti S, Procopio V, et al. Lack of clear and univocal genotype-phenotype correlation in familial Mediterranean fever patients: a systematic review. Clin Genet 2018;94:81-94. doi: 10.1111/cge.13223
  • 7. Ayaz NA, Tanatar A, Karadag SG, et al. Comorbidities and phenotype-genotype correlation in children with familial Mediterranean fever. Rheumatol Int 2021;41:113-20. doi: 10.1007/s00296-020-04592-7
  • 8. Ben-Chetnt E, Levy M. Familial Meditarrenan Fever. Lancet 1998;351:659-64. doi: 10.1016/S0140-6736(97)09408-7
  • 9. Ozen S, Batu ED. The myths we believed in familial Mediterranean fever: what have we learned in the past years? Semin Immuno pathol 2015;37:363-9. doi: 10.1007/s00281-015-0484-6
  • 10. Akin H, Onay H, Turker E, Cogulu O, Ozkinay F. MEFV mutations in patients with Familial Mediterranean Fever from the Aegean region of Turkey. Mol Biol Rep 2010; 37:93-8. doi: 10.1007/s11033-009-9543-1
  • 11. Ben-Chetrit E, Yazici H. Familial Mediterranean fever: different faces around the world. Clin Exp Rheumatol 2019;121:18-22.
  • 12. Livneh A, Langevitz P, Zemer D, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997;40:1879-85. doi: 10.1002/art.1780401023
  • 13. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373-83. doi: 10.1016/0021-9681(87)90171-8
  • 14. Migita K, Agematsu K, Yazaki M, et al. Familial Mediterranean fever: genotypephenotype correlations in Japanese patients. Medicine 2014;93:158-64. doi: 10.1097/MD.0000000000000029
  • 15. Samuels J, Aksentıjevıch I, Torosyan Y, et al. Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine 1998;77:268-97. doi: 10.1097/00005792-199807000-00005
  • 16. Sari I, Birlik M, Kasifoglu T. Familial Mediterranean fever: an updated review. Eur J Rheumatol 2014;1:21-33. doi: 10.5152/eurjrheum.2014.006
  • 17. Yasar Bilge NS, Bodakcı E, Bilge U, Kasifoğlu T. Gender is not a Prognostic Factor for Familial Mediterranean Fever. Ankara Med J 2019;4:716-21. doi: 10.17098/amj.651961
  • 18. Tunca M, Akar S, Onen F, et al. Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 2005;84:1-11. doi: 10.1097/01.md.0000152370.84628.0c
  • 19. Dewalle M, Domingo C, Rozenbaum M, et al. Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF). Eur J Hum Genet 1998;6: 95-7. doi: 10.1038/ sj.ejhg.5200170
  • 20.Kunt SS, Aydin F, Cakar N, Ozdel S, et al. The effect ofgenotype on musculoskeletal complaints in patients with familial Mediterranean fever. Postgrad Med 2020;132:220-4. doi: 10.1080/00325481.2019.1708147
  • 21.Özdel S, Özçakar ZB, Kunt SS, Elhan AH, Yalçinkaya F. Late-onset disease is associated with a mild phenotype in children with familial Mediterranean fever. Clin Rheumatol 2016;35:1837-40. doi: 10.1007/s10067-016-3196-y
  • 22.Barut K, Sahin S, Adrovic A, et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatol Int 2018;38:67-74. doi: 10.1007/s00296-017-3796-0
  • 23.Öztürk K, Çakan M. The analysis of genotype-phenotypecorrelation in familial Mediterranean fever. Pediatr Int2022;64:e15017. doi: 10.1111/ped.15017
  • 24.Öztürk K, Çakan M. Protracted febrile myalgia syndrome as the first manifestation of familial Mediterranean fever in children: case-based review. Rheumatol Int 2021; 41:213-8. doi: 10.1007/s00296-020-04696-0
  • 25.Hotta Y, Kawasaki T, Kotani T, et al. Familial Mediterranean fever without fever. Intern Med 2020; 59:1267-70. doi: 10.2169/internalmedicine.3175-19
  • 26.Blomqvist A, Engblom D. Neural mechanisms of inflammation-induced fever. Neuroscientist 2018;24:381-99. doi: 10.1177/1073858418760481
  • 27.Engström L, Ruud J, Eskilsson A, et al. Lipopolysaccharide-induced fever depends on prostaglandin E2 production specifically in brain endothelial cells. Endocrinology 2012;153:4849–61. doi: 10.1210/en.2012-1375
  • 28.Öztürk K, Coşkuner T, Baglan, et al. Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort. Front Pediatr 2022;9:805919. doi: 10.3389/fped.2021.805919
  • 29.Mukhin NA, Kozlovskaya LV, Bogdanova MV et al. Predictors of AA amyloidosis in familial Mediterranean fever. Rheumatol Int 2015;35:1257-61. doi:10.1007/s00296-014-3205-x
  • 30.Yasar Bilge NS, Sari I, Solmaz D, et al. Comparison of early versus late onset familial Mediterranean fever. Int J Rheum Dis 2018;21:880-4. doi: 10.1111/1756-185X.13259
  • 31.Sonmez HE, Esmeray P, Batu ED, et al. Is age associated with disease severity and compliance to treatment in children with familial Mediterranean fever? Rheumatol Int 2019;39:83-7. doi: 10.1007/s00296-018-4123-0
  • 32.Kasifoglu T, Bilge SY, Sari I et al. Amyloidosis and its relatedfactors in Turkish patients with familial Mediterranean fever: amulticentre study. Rheumatology (Oxford) 2014;53:741-5. doi: 10.1093/rheumatology/ket400
  • 33.Cazeneuve C, Ajrapetyan H, Papin S, et al. Identification ofMEFV-independent modifying genetic factors for familial Mediterranean fever. Am J Hum Genet 2000;67:1136-43. doi: 10.1016/S0002-9297(07)62944-9
  • 34.Gershoni‐Baruch R, Brik R, Zacks N, et al. The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever.Arthritis Rheum 2003;48:1149-55. doi: 10.1002/art.10944
  • 35.Parmaksız G, Noyan ZA. Can RDW be used as a screening test for subclinical infammation in children with FMF? Is RDW related to MEFV gene mutations? Clin Rheumatol 2023;42:197-202. doi:10.1007/s10067-022-06358-x
  • 36.Van der Hilst JCH, Simon A, Drenth JPH. Hereditary periodicfever and reactive amyloidosis. Clin Exp Med 2005;5:87-98 doi: 10.1007/s10238-005-0071-6
There are 36 citations in total.

Details

Primary Language Turkish
Subjects Rheumatology and Arthritis
Journal Section Research Article
Authors

Tuğba Ocak 0000-0002-4560-1569

Ahmet Görünen 0000-0002-7745-8226

Burcu Yağız 0000-0002-0624-1986

Belkıs Nihan Coşkun 0000-0003-0298-4157

Şebnem Özemri Sağ 0000-0002-3948-8889

Hüseyin Ediz Dalkılıç 0000-0001-8645-2670

Yavuz Pehlivan 0000-0002-7054-5351

Publication Date May 17, 2024
Submission Date December 27, 2023
Acceptance Date April 3, 2024
Published in Issue Year 2024 Volume: 50 Issue: 1

Cite

APA Ocak, T., Görünen, A., Yağız, B., Coşkun, B. N., et al. (2024). Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 50(1), 29-33. https://doi.org/10.32708/uutfd.1410535
AMA Ocak T, Görünen A, Yağız B, Coşkun BN, Özemri Sağ Ş, Dalkılıç HE, Pehlivan Y. Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması. Uludağ Tıp Derg. May 2024;50(1):29-33. doi:10.32708/uutfd.1410535
Chicago Ocak, Tuğba, Ahmet Görünen, Burcu Yağız, Belkıs Nihan Coşkun, Şebnem Özemri Sağ, Hüseyin Ediz Dalkılıç, and Yavuz Pehlivan. “Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik Ve Laboratuvar Yansıması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50, no. 1 (May 2024): 29-33. https://doi.org/10.32708/uutfd.1410535.
EndNote Ocak T, Görünen A, Yağız B, Coşkun BN, Özemri Sağ Ş, Dalkılıç HE, Pehlivan Y (May 1, 2024) Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50 1 29–33.
IEEE T. Ocak, “Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması”, Uludağ Tıp Derg, vol. 50, no. 1, pp. 29–33, 2024, doi: 10.32708/uutfd.1410535.
ISNAD Ocak, Tuğba et al. “Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik Ve Laboratuvar Yansıması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 50/1 (May 2024), 29-33. https://doi.org/10.32708/uutfd.1410535.
JAMA Ocak T, Görünen A, Yağız B, Coşkun BN, Özemri Sağ Ş, Dalkılıç HE, Pehlivan Y. Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması. Uludağ Tıp Derg. 2024;50:29–33.
MLA Ocak, Tuğba et al. “Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik Ve Laboratuvar Yansıması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, vol. 50, no. 1, 2024, pp. 29-33, doi:10.32708/uutfd.1410535.
Vancouver Ocak T, Görünen A, Yağız B, Coşkun BN, Özemri Sağ Ş, Dalkılıç HE, Pehlivan Y. Ailevi Akdeniz Ateşi Tanısı Olan Hastalarda Ekzon 10 Lokasyonunda Mutasyon Pozitifliğinin Klinik ve Laboratuvar Yansıması. Uludağ Tıp Derg. 2024;50(1):29-33.
 Download Cover Image

ISSN: 1300-414X, e-ISSN: 2645-9027

Uludağ Üniversitesi Tıp Fakültesi Dergisi "Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License" ile lisanslanmaktadır.


Creative Commons License
Journal of Uludag University Medical Faculty is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

2023