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

Karaka�, Zeynep; Ko�, Beg�m; Temurhan, Sonay; Elg�n, Tu�ba; Karaman, Serap; Asker, Gamze; Gen�ay, Genco; Timur, �etin; Y�ld�rmak, Zeynep Y�ld�z; Celkan, T�raje; Devecioglu, Omer; Ayd�n, Filiz

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

Zeynep Karaka�¹, Beg�m Ko�¹, Sonay Temurhan², Tu�ba Elg�n², Serap Karaman¹, Gamze Asker³, Genco Gen�ay³, �etin Timur⁴, Zeynep Y�ld�z Y�ld�rmak⁵, T�raje Celkan⁶, Omer Devecioglu¹, Filiz Ayd�n²
¹�stanbul University �stanbul Faculty of Medicine, Department of Pediatric Hematology-Oncology, �stanbul, Turkey
²�stanbul University �stanbul Faculty of Medicine, Department of Medical Biology, �stanbul, Turkey
³�stanbul University �stanbul Faculty of Medicine, Department of Pediatrics, �stanbul, Turkey
⁴G�ztepe Education and Research Hospital, Clinic of Pediatric Hematology, �stanbul, Turkey
⁵�i�li Etfal Education and Research Hospital, Clinic of Pediatric Hematology, �stanbul, Turkey
⁶�stanbul University Cerrahpa�a Faculty of Medicine, Department of Pediatric Hematology-Oncology, �stanbul, 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 Paks�) 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 Mutasyonlar�n�n De�erlendirmesi: �stanbul Perspekti

G�R�� ve AMA�: Alfa talasemi sendromlar�, bir ya da daha fazla α-globin genindeki mutasyonlardan kaynaklan�r. Mutasyonlar genelikle delesyonel olmakla birlikte non-delesyonel de olabilir. Baz� delesyonlar (3.7 ve 4.2) α+-talasemiye neden olurken baz�lar� da (-20.5, MED, THAI, FIL) α0-talasemiye yol a�ar. Bu �al��ma ile �stanbul ilinde, di�er nedenlerle a��klanamayan hipokrom mikrositer anemili olgularda alfa talasemi mutasyonlar�n� belirlemeyi ve mutasyon tiplerini de�erlendirmeyi ama�lad�k.
Y�NTEM ve GERE�LER: Bu �al��mada 206 hasta alfa talasemi i�in de�erlendirmeye al�nd�. Her hastadan DNA izolasyonu i�in 2 ml ven�z kan �rne�i al�nd�. Strip analiz kiti (ViennaLab Diagnostics GmbH, Austria) kullan�larak alfa talasemi mutasyonlar� ara�t�r�ld�.
BULGULAR: Doksan be� hastada (%46,1) 14 farkl� mutasyon tespit edildi. En s�k saptanan mutasyon 3.7 tek gen delesyonu idi (n=37 hasta, %39). Di�er mutasyonlar s�kl�k s�ras�na g�re; 20,5 kb �ift gen delesyonu (n=20, %21), MED �ift 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 (T�rk tipi) (n=1) hastalar�n %1�inde saptand�. Yedi hasta alfa talasemi gen triplikasyonu (%7,4) ta��yordu. �al��mam�zda �� mutasyon (Hb Icaria, α1 cd14, α2 init.cd) T�rkiye�de ilk kez tespit edildi. Yedi mutasyon ise (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paks�) hastalar�m�zda hi� saptanmad�.
TARTI�MA ve SONU�: Alfa talasemi, hipokrom mikrositer anemilerin ay�r�c� tan�s�nda �zellikle de demir eksikli�i ve beta-talasemi ta��y�c�l��n�n saptanmad�� durumlarda akla getirilmelidir. ��pheli olgularda genetik a��dan mutasyon taramas� yap�lmal�d�r. Alfa talasemi taramas�n� daha uygun maliyetle yapabilmek i�in T�rkiye�de saptanan t�m alfa talasemi mutasyonlar�n�n topland�� ulusal bir veritaban� olu�turulmas�n� �nermekteyiz.

Anahtar Kelimeler: Alfa talasemi, Anemi, Hb Adana, Hb Icaria, Hb Koya Dora, Mutasyon, Talasemi

Zeynep Karaka�, Beg�m Ko�, Sonay Temurhan, Tu�ba Elg�n, Serap Karaman, Gamze Asker, Genco Gen�ay, �etin Timur, Zeynep Y�ld�z Y�ld�rmak, T�raje Celkan, Omer Devecioglu, Filiz Ayd�n. Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The �stanbul Perspective. Turk J Hematol. 2015; 32(4): 344-350

Corresponding Author: Beg�m Ko�, T�rkiye

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