Araştırma Makalesi
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Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey

Yıl 2021, Cilt: 6 Sayı: 3, 105 - 110, 30.08.2021

Burcu Akıncı Fatma Demir Ebru Tuncez Özlem Öz

https://doi.org/10.22391/fppc.805164

Öz

Introduction: Beta-thalassemia is an autosomal recessive disease that occurs as a result of a disorder in the (β-globin chains synthesis), and the gold standard method for diagnosis is genetic mutation analysis. It is important to know the distribution of mutations according to regions and races. The aim of this study is to document the mutations in the beta-globin gene of beta-thalassemia major and intermedia patients who were followed and treated in Sanliurfa province, and to examine the relationships between these mutations by defining them according to gender, nationality, consanguineous marriage, history of disease in siblings and blood type.

Methods: The files of 272 patients diagnosed with beta-thalassemia major and intermedia followed up in the Pediatric Hematology-Oncology outpatient clinic of Sanliurfa Training and Research Hospital between August 2016 and August 2017 were retrospectively reviewed and mutation analyzes were documented. Coding exons and exon-intron junction regions of beta globin-HBB gene were amplified by PCR method and then DNA sequencing was performed. Gender, nationality, consanguineous marriage, sibling history and blood type information were recorded.

Results: Out of 272 patients, 94.1% were thalassemia major and the others were thalassemia intermedia. Approximately one third of the patients (30.1%) were foreign nationals. A total of 27 different mutations in the beta-globin gene were detected. The most common mutation is IVS-I-110 c.93-21 (G> A) (23.1%), which is followed by IVS-I-1 c.92 + 1 (G> A) (15.8%) and Codon 39 c.118 (C> T) (11.5%). One hundred and forty-two individuals (52.2%) had no sibling history, while 103 (37.9%) had one sibling and 27 (9.9%) had two siblings with thalassemia disorder. First-degree, second degree and third degree consanguineous marriages were present in 42.6% (n = 116), 8.1% (n = 22), 11% (n = 30) of parents, respectively.

Conclusions: Beta-thalassemia disease is a common hematological condition in Sanliurfa. Approximately one-third of the patients who apply are foreign nationals. Correct identification of beta-globin gene mutations will guide genetic counseling and preventing prenatal disease. This data can contribute to the national thalassemia prevention program in Turkey.

Anahtar Kelimeler

beta-thalassemia major beta-thalassemia intermedia mutation consanguineous marriage

Kaynakça

  • 1. Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014;38(5): 305-7. https://doi.org/10.3109/03630269.2014.938163
  • 2. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6. https://doi.org/10.1182/blood-2010-01-251348
  • 3. Canatan D, Aydinok Y. [Thalassemia and hemoglobinopathies diagnosis and treatment book] (in Turkish), 1st ed. Antalya. Thalassaemia Federation, 2007.
  • 4. Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet 2018; 391(10116):155–67. https://doi.org/10.1016/S0140-6736(17)31822-6
  • 5. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet. 2012; 379(9813):373–83. https://doi.org/10.1016/S0140-6736(11)60283-3
  • 6. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118(13):3479–88. https://doi.org/10.1182/blood-2010-08-300335
  • 7. Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12(2):61-76. https://doi.org/10.1097/GIM.0b013e3181cd68ed
  • 8. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: Revisited. Blood Cells Mol. Dis. 2006;37(1):12-20. https://doi.org/10.1016/j.bcmd.2006.04.005
  • 9. Canatan D, Kose MR, Ustundag M, Haznedaroglu D, Ozbas S. Hemoglobinopathy control program in Turkey. Community Genet. 2006;9(2):124-6. https://doi.org/10.1159/000091493
  • 10. Giardine B, Borg J, Viennas E, Pavlidis C, Moradkhani K, Jolly P, et al. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res. 2014;42(D1):1063-9. https://doi.org/10.1093/nar/gkt911
  • 11. Cappellini MD, Cohen A, Porter J, Viprakasit V. Guidelines for the management of transfusion dependent thalassaemia (TDT), 3rd ed. Nicosia, Thalassaemia International Federation, 2014.
  • 12. Aydinok Y, Oymak Y, Atabay B, Aydogan G, Yesilipek A, Unal S, et al. A National registry of thalassemia in Turkey: demographic and disease characteristics of patients, achievements, and challenges in prevention. Turk J Hematol 2018;35(1):12-8. https://doi.org/10.4274/tjh.2017.0039
  • 13. Basak AN. The molecular pathology of beta-thalassemia in Turkey: The Bogazici University experience. Hemoglobin. 2007;31(2):233-41. https://doi.org/10.1080/03630260701296735
  • 14. Akar N, Cavdar AO, Dessi E, Loi A, Pirastu M, Cao A. Beta thalassaemia mutations in the Turkish population. J Med Genet. 1987;24(6):378–81. https://doi.org/10.1136/jmg.24.6.378
  • 15. Fettah A, Bayram C, Yarali N, Isik P, Kara A, Culha V, et al. Beta-globin gene mutation in Turkish children with beta-thalassemia: results from a single center study. Mediterr J Hematol Infect Dis. 2013;5(1):e2013055. https://doi.org/10.4084/MJHID.2013.055
  • 16. Altay C. The frequency and distribution pattern of beta-thalassemia mutations in Turkey. Turkish J Haematol. 2002;19(2):309-15. https://ncbi.nlm.nih.gov/pubmed/27264774
  • 17. Kayahan M, Simsek Z, Ersin F, Gozukara F, Kurcer MA. [Prevalence of consanguineous marriage and its effect on deaths under 5 years of age in Sanliurfa Tilfindir Health Center] (in Turkish). C.U. Hemsire Yuksek Derg. 2003;7(1):1-4. https://dergipark.org.tr/tr/pub/dtfd/issue/48273/611151
  • 18. Mondal B, Maiti S, Biswas BK, Ghosh D, Paul S. Prevalence of hemoglobinopathy, ABO and rhesus blood groups in rural areas of West Bengal, India. J Res Med Sci. 2012; 17(8):772-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687885
  • 19. De Sanctis V, Kattamis C, Canatan D, Soliman AT, Elsedfy H, Karimi M, et al. β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017;9(1):e2017018. https://doi.org/10.4084/mjhid.2017.018
  • 20. Syrian Regional Response—Inter-agency Information sharing Portal [Internet]. Available from: https://data2.unhcr.org/en/situations/syria/location/113 (Date of access:22.09.2020)
  • 21. Aras B, Duman Y. I/NGOs’ Assistance to Syrian Refugees in Turkey: Opportunities and Challenges. J Balk Near East Stud. 2019;21(4):478-91. https://doi.org/10.1080/19448953.2018.1530382
  • 22. Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of β-thalassemia. Eur J Haematol. 2020;00:1-12. https://doi.org/10.1111/ejh.13512
  • 23. Aycicek A, Koc A, Ozdemir ZC, Bilinc H, Kocyigit A, Dilmec F. Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey. Turk J Hematol 2011;28(4):264-8. https://doi.org/10.5152/tjh.2011.86

Türkiye, Şanlıurfa’da Beta-Talasemi mutasyon çeşitleri ve demografik faktörlerle ilişkisi

Yıl 2021, Cilt: 6 Sayı: 3, 105 - 110, 30.08.2021

Burcu Akıncı Fatma Demir Ebru Tuncez Özlem Öz

https://doi.org/10.22391/fppc.805164

Öz

Giriş: Beta-talasemi, β-globin zincir sentezindeki bir bozukluk sonucu ortaya çıkan otozomal resesif geçişli bir hastalık olup, tanı koyabilmek için altın standart yöntem genetik mutasyon analizidir. Bölgelere ve ırklara göre mutasyon dağılımlarının bilinmesi önem taşımaktadır. Bu araştırmanın amacı, Şanlıurfa ilinde takip ve tedavi edilen beta-talasemi majör ve intermedia hastalarının beta-globin geninde bulunan mutasyonları dökümante etmek ve bu mutasyonların cinsiyet, uyruk, akraba evliliği, kardeşte hastalık öyküsü ve kan grubuna göre tanımlamasını yaparak aradaki ilişkileri incelemektir.

Yöntem: Şanlıurfa Eğitim ve Araştırma Hastanesi Çocuk Hematoloji-Onkoloji polikliniğinde Ağustos 2016-Ağustos 2017 takip edilen beta-talasemi majör ve intermedia tanılı 272 hastanın dosyaları retrospektif olarak taranarak mutasyon analizleri dökümante edildi. Mutasyon analizleri, Beta globin-HBB geninin kodlama yapan ekzonları ve ekzon-intron bağlantı bölgeleri PCR yöntemi ile amplifiye edildikten sonra DNA dizi analizi ile yapıldı. Cinsiyet, uyruk, akraba evliliği, kardeş öyküsü ve kan grubu bilgileri kaydedildi.

Bulgular: İki yüz yetmiş iki hastanın %94,1’ini talasemi majör, diğerlerini talasemi intermedia olguları oluşturmaktaydı. Hastaların yaklaşık üçte biri (%30,1) yabancı uyrukluydu. Beta-globin geninde toplam 27 farklı mutasyon saptandı. En sık görülen mutasyon IVS-I-110 c.93-21 (G>A) (%23,1) olup, bunu IVS-I-1 c.92+1 (G>A)‎ (%15,8) ve Codon 39 c.118 (C>T) (%11,5) takip etmekteydi. Yüz kırk iki kişide (%52,2) kardeş öyküsü bulunmazken 103 kişide (%37,9) bir kardeşte, 27 kişide ise ‎‎(%9,9) iki kardeşte hastalık bulunmaktaydı. Hastaların anne ve babalarının %42,6’sında ‎‎(n=116) birinci derece, %8,1’inde (n=22) ikinci derece, %11’inde (n=30) ise ‎üçüncü derece akraba evliliği söz konusu idi.‎

Sonuç: Şanlıurfa’da beta-talasemi hastalığı, sık görülen bir hematolojik durumdur. Başvuran hastaların yaklaşık üçte biri yabancı uyrukludur. Beta-globin gen mutasyonlarının doğru tanımlanması genetik danışma ve doğum öncesi hastalığın engellenebilmesi açısından yol gösterici olacaktır. Bu veriler, Türkiye’de ulusal talasemi önleme programına katkı sağlayabilir.

Anahtar Kelimeler

beta-talasemi majör beta-talasemi intermedia mutasyon akraba evliliği

Kaynakça

  • 1. Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014;38(5): 305-7. https://doi.org/10.3109/03630269.2014.938163
  • 2. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6. https://doi.org/10.1182/blood-2010-01-251348
  • 3. Canatan D, Aydinok Y. [Thalassemia and hemoglobinopathies diagnosis and treatment book] (in Turkish), 1st ed. Antalya. Thalassaemia Federation, 2007.
  • 4. Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet 2018; 391(10116):155–67. https://doi.org/10.1016/S0140-6736(17)31822-6
  • 5. Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet. 2012; 379(9813):373–83. https://doi.org/10.1016/S0140-6736(11)60283-3
  • 6. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118(13):3479–88. https://doi.org/10.1182/blood-2010-08-300335
  • 7. Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12(2):61-76. https://doi.org/10.1097/GIM.0b013e3181cd68ed
  • 8. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: Revisited. Blood Cells Mol. Dis. 2006;37(1):12-20. https://doi.org/10.1016/j.bcmd.2006.04.005
  • 9. Canatan D, Kose MR, Ustundag M, Haznedaroglu D, Ozbas S. Hemoglobinopathy control program in Turkey. Community Genet. 2006;9(2):124-6. https://doi.org/10.1159/000091493
  • 10. Giardine B, Borg J, Viennas E, Pavlidis C, Moradkhani K, Jolly P, et al. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res. 2014;42(D1):1063-9. https://doi.org/10.1093/nar/gkt911
  • 11. Cappellini MD, Cohen A, Porter J, Viprakasit V. Guidelines for the management of transfusion dependent thalassaemia (TDT), 3rd ed. Nicosia, Thalassaemia International Federation, 2014.
  • 12. Aydinok Y, Oymak Y, Atabay B, Aydogan G, Yesilipek A, Unal S, et al. A National registry of thalassemia in Turkey: demographic and disease characteristics of patients, achievements, and challenges in prevention. Turk J Hematol 2018;35(1):12-8. https://doi.org/10.4274/tjh.2017.0039
  • 13. Basak AN. The molecular pathology of beta-thalassemia in Turkey: The Bogazici University experience. Hemoglobin. 2007;31(2):233-41. https://doi.org/10.1080/03630260701296735
  • 14. Akar N, Cavdar AO, Dessi E, Loi A, Pirastu M, Cao A. Beta thalassaemia mutations in the Turkish population. J Med Genet. 1987;24(6):378–81. https://doi.org/10.1136/jmg.24.6.378
  • 15. Fettah A, Bayram C, Yarali N, Isik P, Kara A, Culha V, et al. Beta-globin gene mutation in Turkish children with beta-thalassemia: results from a single center study. Mediterr J Hematol Infect Dis. 2013;5(1):e2013055. https://doi.org/10.4084/MJHID.2013.055
  • 16. Altay C. The frequency and distribution pattern of beta-thalassemia mutations in Turkey. Turkish J Haematol. 2002;19(2):309-15. https://ncbi.nlm.nih.gov/pubmed/27264774
  • 17. Kayahan M, Simsek Z, Ersin F, Gozukara F, Kurcer MA. [Prevalence of consanguineous marriage and its effect on deaths under 5 years of age in Sanliurfa Tilfindir Health Center] (in Turkish). C.U. Hemsire Yuksek Derg. 2003;7(1):1-4. https://dergipark.org.tr/tr/pub/dtfd/issue/48273/611151
  • 18. Mondal B, Maiti S, Biswas BK, Ghosh D, Paul S. Prevalence of hemoglobinopathy, ABO and rhesus blood groups in rural areas of West Bengal, India. J Res Med Sci. 2012; 17(8):772-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687885
  • 19. De Sanctis V, Kattamis C, Canatan D, Soliman AT, Elsedfy H, Karimi M, et al. β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017;9(1):e2017018. https://doi.org/10.4084/mjhid.2017.018
  • 20. Syrian Regional Response—Inter-agency Information sharing Portal [Internet]. Available from: https://data2.unhcr.org/en/situations/syria/location/113 (Date of access:22.09.2020)
  • 21. Aras B, Duman Y. I/NGOs’ Assistance to Syrian Refugees in Turkey: Opportunities and Challenges. J Balk Near East Stud. 2019;21(4):478-91. https://doi.org/10.1080/19448953.2018.1530382
  • 22. Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of β-thalassemia. Eur J Haematol. 2020;00:1-12. https://doi.org/10.1111/ejh.13512
  • 23. Aycicek A, Koc A, Ozdemir ZC, Bilinc H, Kocyigit A, Dilmec F. Beta-globin gene mutations in children with beta-thalassemia major from Sanliurfa province, Turkey. Turk J Hematol 2011;28(4):264-8. https://doi.org/10.5152/tjh.2011.86
Toplam 23 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Çocuk Sağlığı ve Hastalıkları
Bölüm Araştırma Makalesi (Original Article)
Yazarlar

Burcu Akıncı 0000-0001-6026-4786

Fatma Demir 0000-0001-8692-2767

Ebru Tuncez 0000-0002-0258-7779

Özlem Öz 0000-0002-5533-6025

Yayımlanma Tarihi 30 Ağustos 2021
Gönderilme Tarihi 5 Ekim 2020
Kabul Tarihi 18 Mart 2021
Yayımlandığı Sayı Yıl 2021Cilt: 6 Sayı: 3

Kaynak Göster

APA Akıncı, B., Demir, F., Tuncez, E., Öz, Ö. (2021). Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey. Family Practice and Palliative Care, 6(3), 105-110. https://doi.org/10.22391/fppc.805164
AMA Akıncı B, Demir F, Tuncez E, Öz Ö. Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey. Fam Pract Palliat Care. Aralık 2021;6(3):105-110. doi:10.22391/fppc.805164
Chicago Akıncı, Burcu, Fatma Demir, Ebru Tuncez, ve Özlem Öz. “Beta-Thalassemia Mutation Types and the Relationship With the Demographic Factors in Sanliurfa, Turkey”. Family Practice and Palliative Care 6, sy. 3 (Aralık 2021): 105-10. https://doi.org/10.22391/fppc.805164.
EndNote Akıncı B, Demir F, Tuncez E, Öz Ö (01 Aralık 2021) Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey. Family Practice and Palliative Care 6 3 105–110.
IEEE B. Akıncı, F. Demir, E. Tuncez, ve Ö. Öz, “Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey”, Fam Pract Palliat Care, c. 6, sy. 3, ss. 105–110, 2021, doi: 10.22391/fppc.805164.
ISNAD Akıncı, Burcu vd. “Beta-Thalassemia Mutation Types and the Relationship With the Demographic Factors in Sanliurfa, Turkey”. Family Practice and Palliative Care 6/3 (Aralık 2021), 105-110. https://doi.org/10.22391/fppc.805164.
JAMA Akıncı B, Demir F, Tuncez E, Öz Ö. Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey. Fam Pract Palliat Care. 2021;6:105–110.
MLA Akıncı, Burcu vd. “Beta-Thalassemia Mutation Types and the Relationship With the Demographic Factors in Sanliurfa, Turkey”. Family Practice and Palliative Care, c. 6, sy. 3, 2021, ss. 105-10, doi:10.22391/fppc.805164.
Vancouver Akıncı B, Demir F, Tuncez E, Öz Ö. Beta-thalassemia mutation types and the relationship with the demographic factors in Sanliurfa, Turkey. Fam Pract Palliat Care. 2021;6(3):105-10.

Family Practice and Palliative Care      ISSN 2458-8865       E-ISSN 2459-1505