ISSN: 1300-7777 E-ISSN: 1308-5263
Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective [Turk J Hematol]
Turk J Hematol. 2015; 32(4): 344-350 | DOI: 10.4274/tjh.2014.0204  

Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective

Zeynep Karakaş1, Begüm Koç1, Sonay Temurhan2, Tuğba Elgün2, Serap Karaman1, Gamze Asker3, Genco Gençay3, Çetin Timur4, Zeynep Yıldız Yıldırmak5, Tıraje Celkan6, Omer Devecioglu1, Filiz Aydın2
1İstanbul University İstanbul Faculty of Medicine, Department of Pediatric Hematology-Oncology, İstanbul, Turkey
2İstanbul University İstanbul Faculty of Medicine, Department of Medical Biology, İstanbul, Turkey
3İstanbul University İstanbul Faculty of Medicine, Department of Pediatrics, İstanbul, Turkey
4Göztepe Education and Research Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
5Şişli Etfal Education and Research Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
6İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Hematology-Oncology, İstanbul, Turkey

INTRODUCTION: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -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.
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 α-thalassemia mutations by using the Vienna Lab α-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%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study.
DISCUSSION AND CONCLUSION: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and β-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.

Keywords: Anemia, Alpha thalassemia, Hb Adana, Hb Icaria, Hb Koya Dora, Mutation, Thalassemia


Hipokromik Mikrositer Anemili Olgularda Alfa Talasemi Mutasyonlarının Değerlendirmesi: İstanbul Perspekti

Zeynep Karakaş1, Begüm Koç1, Sonay Temurhan2, Tuğba Elgün2, Serap Karaman1, Gamze Asker3, Genco Gençay3, Çetin Timur4, Zeynep Yıldız Yıldırmak5, Tıraje Celkan6, Omer Devecioglu1, Filiz Aydın2
1İstanbul University İstanbul Faculty of Medicine, Department of Pediatric Hematology-Oncology, İstanbul, Turkey
2İstanbul University İstanbul Faculty of Medicine, Department of Medical Biology, İstanbul, Turkey
3İstanbul University İstanbul Faculty of Medicine, Department of Pediatrics, İstanbul, Turkey
4Göztepe Education and Research Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
5Şişli Etfal Education and Research Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey
6İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Hematology-Oncology, İstanbul, Turkey

GİRİŞ ve AMAÇ: Alfa talasemi sendromları, bir ya da daha fazla α-globin genindeki mutasyonlardan kaynaklanır. Mutasyonlar genelikle delesyonel olmakla birlikte non-delesyonel de olabilir. Bazı delesyonlar (3.7 ve 4.2) α+-talasemiye neden olurken bazıları da (-20.5, MED, THAI, FIL) α0-talasemiye yol açar. Bu çalışma ile İstanbul ilinde, diğer nedenlerle açıklanamayan hipokrom mikrositer anemili olgularda alfa talasemi mutasyonlarını belirlemeyi ve mutasyon tiplerini değerlendirmeyi amaçladık.
YÖNTEM ve GEREÇLER: 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), α2 IVS1 (n=10, %10,5), α2 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 α1 cd 14 (n=2, %2,1) idi. Hb Adana (n=1), Hb Ikaria (n=1), α2 init cd (n=1) ve α2 poly-A2 (Türk tipi) (n=1) hastaların %1’inde saptandı. Yedi hasta alfa talasemi gen triplikasyonu (%7,4) taşıyordu. Çalışmamızda üç mutasyon (Hb Icaria, α1 cd14, α2 init.cd) Türkiye’de ilk kez tespit edildi. Yedi mutasyon ise (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) hastalarımızda hiç saptanmadı.
TARTIŞMA ve 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 Kelimeler: Alfa talasemi, Anemi, Hb Adana, Hb Icaria, Hb Koya Dora, Mutasyon, Talasemi


Zeynep Karakaş, Begüm Koç, Sonay Temurhan, Tuğba Elgün, Serap Karaman, Gamze Asker, Genco Gençay, Çetin Timur, Zeynep Yıldız Yıldırmak, Tıraje Celkan, Omer Devecioglu, Filiz Aydın. Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective. Turk J Hematol. 2015; 32(4): 344-350

Corresponding Author: Begüm Koç, Türkiye


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