Description of hematologic and molecular genetic features of beta-thalassemia in laboratory practice

Introduction. Beta-thalassemia is one of the most common inherited disorders characterized by reduced or complete absence of beta-globin chain synthesis. The CBC parameters of patients with beta-thalassemia are often similar to other microcytic hypochromic anemias, which makes it difficult to use these parameters for the purpose of differential diagnosis of anemias. The prevalence of beta-thalassemia is increasing in non-endemic regions, including the Russian Federation. However, in our country, the prevalence, laboratory and molecular genetic features of beta-thalassemia remain insufficiently studied.
Objective: to characterize hematological and molecular genetic features of beta-thalassemia in laboratory practice.
Methods. The present study examined the results of CBC of 58266 patients over 18 years of age. Patients with hemoglobin and/or mean corpuscular volume and/or mean corpuscular hemoglobin values below the reference values were selected according to the results of a complete blood count. Mentzer and Sirdah’s calculated indices were utilised for further differentiation. Patients with both indices below the threshold values were subjected to direct automatic Sanger sequencing of the HBB gene.
Results. Among 58266 patients, 20040 (34.39%) had Hb and/or MCV and/or MCH values below reference values. Values of both calculated indices indicated beta-thalassemia in 182 patients (0.91% among patients with CBC changes, 0.31% among all subjects). Using the Sanger direct automatic sequencing method, pathogenic variants of the HBB gene were identified in 64 patients, which is 0.32% among patients with CBC changes or 0.109% among all examined individuals. The most common pathogenic variant of the HBB gene in this study is c.25_26del (rs35497102) (21.8%).
Conclusions. A total of 20 different pathogenic variants located in all regions of the HBB gene were detected in this study, which underlines the necessity of studying the nucleotide sequence of the entire gene in the diagnosis of beta-thalassemia using molecular genetic methods. The findings of this study demonstrate that the utilisation of CBC and calculated erythrocyte indices possesses the capacity to categorise patients into distinct risk groups; nevertheless, these methodologies are not characterised by a high degree of sensitivity. The development of more effective methods of differential diagnosis of beta-thalassemia from other microcytic hypochromic anemias is necessary.

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