Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective
Yıl: 2015 Cilt: 32 Sayı: 4 Sayfa Aralığı: 344 - 350 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022
Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective
Öz: Amaç: Alfa talasemi sendromları, bir ya da daha fazla ?-globin genindeki mutasyonlardan kaynaklanır. Mutasyonlar genelikle delesyonel olmakla birlikte non-delesyonel de olabilir. Bazı delesyonlar (3.7 ve 4.2) ?+-talasemiye neden olurken bazıları da (-20.5, MED, THAI, FIL) ?0-talasemiye yol açar. Bu çalışma ile İstanbul ilinde, diğer nedenlerle açıklanamayan hipokrom mikrositer anemili olgularda alfa talasemi mutasyonlarını belirlemeyi ve mutasyon tiplerini değerlendirmeyi amaçladık.Gereç ve Yöntemler: Bu çalışmada 206 hasta alfa talasemi için değerlendirmeye alındı. Her hastadan DNA izolasyonu için 2 ml venöz kan örneği alındı. Strip analiz kiti (ViennaLab Diagnostics GmbH, Austria) kullanılarak alfa talasemi mutasyonları araştırıldı.Bulgular: Doksan beş hastada (%46,1) 14 farklı mutasyon tespit edildi. En sık saptanan mutasyon 3.7 tek gen delesyonu idi (n=37 hasta, %39). Diğer mutasyonlar sıklık sırasına göre; 20,5 kb çift gen delesyonu (n=20, %21), MED çift gen delesyonu (n=17, %17,9), ?2 IVS1 (n=10, %10,5), ?2 poly-A1 (Suudi tip) (n=6, %6,3), Hb Koya Dora (n=6, %6,3), 4.2 tek gen delesyonu (n=4, %4,2), FIL mutasyonu (n=2, %2,1) ve ?1 cd 14 (n=2, %2,1) idi. Hb Adana (n=1), Hb Ikaria (n=1), ?2 init cd (n=1) ve ?2 poly-A2 (Türk tipi) (n=1) hastaların %1'inde saptandı. Yedi hasta alfa talasemi gen triplikasyonu (%7,4) taşıyordu. Çalışmamızda üç mutasyon (Hb Icaria, ?1 cd14, ?2 init.cd) Türkiye'de ilk kez tespit edildi. Yedi mutasyon ise (-SEA, -THAI, Hb Constant Spring, ?2 cd19, ?2 cd59, ?2 cd125, Hb Paksé) hastalarımızda hiç saptanmadı. Sonuç: Alfa talasemi, hipokrom mikrositer anemilerin ayırıcı tanısında özellikle de demir eksikliği ve beta-talasemi taşıyıcılığının saptanmadığı durumlarda akla getirilmelidir. Şüpheli olgularda genetik açıdan mutasyon taraması yapılmalıdır. Alfa talasemi taramasını daha uygun maliyetle yapabilmek için Türkiye'de saptanan tüm alfa talasemi mutasyonlarının toplandığı ulusal bir veritabanı oluşturulmasını önermekteyiz
Anahtar Kelime: Konular:
Hipokromik Mikrositer Anemili Olgularda Alfa Talasemi Mutasyonlarının Değerlendirmesi: İstanbul Perspektifi
Öz: Objective: Alpha thalassemia syndromes are caused by mutations on one or more of the four ?-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause ?+-thalassemia, some cause (-20.5, MED, THAI, FIL) ?0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations.Material and Methods: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for ?-thalassemia mutations by using the Vienna Lab ?-Globlin StripAssay TM commercial kit. Results: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), ?2 IVS1 (n=10 patients, 10.5%), ?2 cd142 Hb Koya Dora (n=6 patients, 6.3%), ?2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), ?1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, ?2 init cd and ?2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had ?-thalassemia triplication. In our study, three mutations (Hb Icaria, ?1 cd14, ?2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, ?2 cd19, ?2 cd59, ?2 cd125, Hb Paksé) were not determined in this study.Conclusion: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and ?-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a national database with all mutations in Turkey should be created to screen the alpha thalassemia cost-effectively
Anahtar Kelime: Konular:
Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- Harteveld CL, Higgs DR. ?-Thalassaemia. Orphanet J Rare Dis 2010;5:13.
- Singer ST. Variable clinical phenotypes of alpha-thalassemia syndromes. Scientific World Journal 2009;9:615-625.
- Kohne E. Hemoglobinopathies: clinical manifestations, diagnosis, and treatment. Dtsch Arztebl Int 2011;108:532- 540.
- Vichinsky EP. Alpha thalassemia major--new mutations, intrauterine management, and outcomes. Hematology Am Soc Hematol Educ Program 2009:35-41.
- Chui DH, Waye JS. Hydrops fetalis caused by alpha- thalassemia: an emerging health care problem. Blood 1998;91:2213-2222.
- Vichinsky EP. Clinical manifestations of ?-thalassemia. Cold Spring Harb Perspect Med 2013;3:011742.
- Galanello R, Cao A. Gene test review. Alpha-thalassemia. Genet Med 2011;13:83-88.
- Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011;118:3479-3488.
- Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008;86:480-487.
- Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ 2001;79:704-712.
- Özsoylu Ş, Malik SA. Incidence of alpha thalassemia in Turkey. Turk J Pediatr 1982;24:235-244.
- Fei YJ, Kutlar F, Harris HF, Wilson MM, Milana A, Sciacca P, Schiliro G, Masala B, Manca L, Altay C, Gurgey A, Huisman TJH. A search for anomalies in the zeta, alpha, beta, and gamma globin gene arrangements in normal black, Italian, Turkish, and Spanish newborns. Hemoglobin 1989;13:45- 65.
- Arcasoy A. Türkiye'de Thalassemia Taşıyıcı Sıklığı. Ankara, Turkey, Ankara Thalassemia Association, 1991 (in Turkish).
- Kılınç Y, Kumi M, Gürgey A, Altay C. Adana Bölgesi'nde doğan bebeklerde kordon kanı çalışması ile ?-talassemi, glukoz- 6-fosfat dehidrogenaz enzim eksikligi ve Hb S sıklığının araştırılması. DOĞA 1986;10:162-167 (in Turkish).
- Canatan D. Türkiye'de hemoglobinopatilerin epidemiyolojisi. HematoLog 2014;4-1:11-23 (in Turkish).
- Canatan D, Oğuz N, Guvendik İ, Yıldırım S. The incidence of alpha-thalassemia in Antalya, Turkey. Turk J Haematol 2002;19:433-434.
- Guvenc B, Yildiz SM, Tekinturhan F, Dincer S, Akyuzluer I, Okten S, Erkman H. Molecular characterization of alpha- thalassemia in Adana, Turkey: a single center study. Acta Haematol 2010;124:197-200.
- Sütçü R, Aylak F, Koçak H, Sipahi T, Vural H, Delibaş N. The investigation of distribution of hereditary alpha-thalassemia mutations in Isparta reservoir. Eur J Basic Med Sci 2011;1:28- 32.
- Celik MM, Gunesacar R, Oktay G, Duran GG, Kaya H. Spectrum of ?-thalassemia mutations including first observation of --FIL deletion in Hatay Province, Turkey. Blood Cells Mol Dis 2013;51:27-30.
- Çürük MA. Hb H (?4) disease in Çukurova, southern Turkey. Hemoglobin 2007;31:265-271.
- Oner C, Gürgey A, Oner R, Balkan H, Gümrük F, Baysal E, Altay C. The molecular basis of Hb H disease in Turkey. Hemoglobin 1997;21:41-51.
- Yüreğir GT, Aksoy K, Çürük MA, Dikmen N, Fei YJ, Baysal E, Huisman TH. Hb H disease in a Turkish family resulting from the interaction of a deletional alpha-thalassemia-1 and newly discovered poly A mutation. Br J Haematol 2008;80:527-532.
- Çürük MA, Kilinç Y, Evrüke C, Özgünen FT, Aksoy K, Yüreğir GT. Prenatal diagnosis of Hb H disease caused by alpha homozygosity for the ?2 poly A(AATAAA-AATAAG) mutation. Hemoglobin 2001;25:255-258.
- Onay H, Aykut A, Karaca E, et al. Ege bölgesinde alfa talasemi mutasyonlarının dağılımının araştırılması. İçinde: 1. Hematolojik Genetik Sempozyumu Bildiri Özet Kitabı, İzmir, Türkiye, 2013, p. 95 (in Turkish).
- Baysal E, Kleanthous M, Bozkurt G, Kyrri A, Kalogirou E, Angastiniotis M, Ioannou P, Huisman TH. Alpha-thalassaemia in the population of Cyprus. Br J Haematol 1995;89:496-499.
- Waye JS, Eng B. Diagnostic testing for a-globin gene disorders in a heterogeneous North American population. Int J Lab Hematol 2013;35:306-313.
| APA | KARAKAS Z, KOÇ B, TEMURHAN S, ELGÜN T, KARAMAN S, ASKER G, GENÇAY G, TİMUR Ç, YILDIZ YILDIRMAK Z, CELKAN T, DEVECİOĞLU Ö, AYDIN F (2015). Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. , 344 - 350. |
| Chicago | KARAKAS ZEYNEP,KOÇ Begüm,TEMURHAN Sonay,ELGÜN TUĞBA,KARAMAN SERAP,ASKER Gamze,GENÇAY Genco,TİMUR Çetin,YILDIZ YILDIRMAK Zeynep,CELKAN TÜLIN TIRAJE,DEVECİOĞLU Ömer,AYDIN Filiz Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. (2015): 344 - 350. |
| MLA | KARAKAS ZEYNEP,KOÇ Begüm,TEMURHAN Sonay,ELGÜN TUĞBA,KARAMAN SERAP,ASKER Gamze,GENÇAY Genco,TİMUR Çetin,YILDIZ YILDIRMAK Zeynep,CELKAN TÜLIN TIRAJE,DEVECİOĞLU Ömer,AYDIN Filiz Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. , 2015, ss.344 - 350. |
| AMA | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. . 2015; 344 - 350. |
| Vancouver | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. . 2015; 344 - 350. |
| IEEE | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F "Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective." , ss.344 - 350, 2015. |
| ISNAD | KARAKAS, ZEYNEP vd. "Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective". (2015), 344-350. |
| APA | KARAKAS Z, KOÇ B, TEMURHAN S, ELGÜN T, KARAMAN S, ASKER G, GENÇAY G, TİMUR Ç, YILDIZ YILDIRMAK Z, CELKAN T, DEVECİOĞLU Ö, AYDIN F (2015). Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turkish Journal of Hematology, 32(4), 344 - 350. |
| Chicago | KARAKAS ZEYNEP,KOÇ Begüm,TEMURHAN Sonay,ELGÜN TUĞBA,KARAMAN SERAP,ASKER Gamze,GENÇAY Genco,TİMUR Çetin,YILDIZ YILDIRMAK Zeynep,CELKAN TÜLIN TIRAJE,DEVECİOĞLU Ömer,AYDIN Filiz Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turkish Journal of Hematology 32, no.4 (2015): 344 - 350. |
| MLA | KARAKAS ZEYNEP,KOÇ Begüm,TEMURHAN Sonay,ELGÜN TUĞBA,KARAMAN SERAP,ASKER Gamze,GENÇAY Genco,TİMUR Çetin,YILDIZ YILDIRMAK Zeynep,CELKAN TÜLIN TIRAJE,DEVECİOĞLU Ömer,AYDIN Filiz Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turkish Journal of Hematology, vol.32, no.4, 2015, ss.344 - 350. |
| AMA | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turkish Journal of Hematology. 2015; 32(4): 344 - 350. |
| Vancouver | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turkish Journal of Hematology. 2015; 32(4): 344 - 350. |
| IEEE | KARAKAS Z,KOÇ B,TEMURHAN S,ELGÜN T,KARAMAN S,ASKER G,GENÇAY G,TİMUR Ç,YILDIZ YILDIRMAK Z,CELKAN T,DEVECİOĞLU Ö,AYDIN F "Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective." Turkish Journal of Hematology, 32, ss.344 - 350, 2015. |
| ISNAD | KARAKAS, ZEYNEP vd. "Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective". Turkish Journal of Hematology 32/4 (2015), 344-350. |
