Analysis of α-thalassemia mutations in patients diagnosed at the Institute of Hematology and Transfusion Medicine

Abstract

Background

Alpha-thalassemia is genetically transmitted hemolytic anemia resulting from disturbance of the globins chain synthesis. Alpha-thalassemia is caused most frequently by deletions and less commonly by nondeletional defects.

Aim

To introduce the molecular methods for routine identifications of alpha-thalassemia mutations and to study the characteristics of these mutations in Poland.

Methods

Blood sample of 155 patients with normal or reduced HbA₂ values was obtained for blood counting. All samples underwent gap-PCR to screen for the seven common α-thal deletions and MLPA analysis. The DNA of 21 patients in which deletions were not detected has been directly sequenced.

Results

We detected mutations in the alpha-globin gene in 72 of 155 patients studied. 55 out of 72 cases showed most common thalassemia deletions, as the following: a single gene deletion (α^3.7 and α^4.2) and both genes deletion (FIL, SEA, MED I, and α^20.5). Owing to the use of MLPA technique, we found nontypical deletions in another 12 patients and multiplication of the alpha-globin genes in further 4 cases. We also identified a patient with a point mutation HBA2: c.300 + 2T>A by DNA sequencing.

Conclusions

Molecular analysis of the alpha-globin cluster is required for a correct diagnosis in patients with normal or reduced level of HbA₂.

The results of the study show that due to the progressive migration of the population and globalization, thalassemia must be included in the differential diagnosis of anemia in Poland.