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

Abstract

Objective: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.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 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.Conclusion:Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-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.

Retrospective Analysis of Alpha Globin Copy Number Variations Determined by Mlpa in the Trakya Region

“…In a study performed by Çelik et al in the southern region of Turkey, -α 3.7 deletion frequency was reported as 43.2% (10). Karakaş et al reported the frequency of -α 3.7 deletion as 39% in a study they performed on patients with hypochromic mi-crocytic anemia living in Istanbul (11). Our data are in accordance with the results of this study carried out in Istanbul, which is located close to the Trakya region.…”

“…-α 4.2 , another type of deletion underlying α + thalassemias, is reported less frequently than the −α 3.7 deletion. Karakaş et al reported the frequency of -α 4.2 deletion as 4.2%, and Onay et al reported that they did not detect any -α 4.2 deletion (6,11). In our study, the -α 4.2 deletion was found in only one case as compound heterozygous with the −α 3.7 deletion.…”

Hemoglobin H Disease in Turkey: Experience from Eight Centers

“…We detected 198 patients with HbH disease when we searched articles from PubMed related to Turkish patients with HbH disease [ 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. When the results of our study were added to that number, we found 471 HbH cases to date from Turkey, and this number is fairly high ( Table 2 ).…”

Hb Adana (HBA2 or HBA1: c.179G > A) and alpha thalassemia: Genotype–phenotype correlation

“…The frequency of Hb Adana varies by country and ethnicity in the thalassemia belt but these reports likely underestimate the true incidence as many patients in these areas do not have access to accurate genetic diagnosis. A low incidence was found in countries such as Turkey (0.5–0.6%), Iran/Iraq (1–2.5%), and China (1%) . Countries found to have a higher prevalence included Saudi Arabia (11.6%) and Indonesia (16%) .…”