Abstract

SCHEPS, Karen Gabriela  and  VARELA, Viviana. Molecular basis of hemoglobinopathies in Argentina. Acta bioquím. clín. latinoam. [online]. 2017, vol.51, n.3, pp.333-342. ISSN 0325-2957.

Functional hemoglobin is a tetramer composed of 2 a and 2 non-a chains, encoded by genes that are organized in clusters and are expressed sequentially through development. There are multiple mutations described that affect these genes: if the sequence variant leads to a qualitative alteration, the resulting effect is a structural hemoglobinopathy, if it decreases the synthesis of the globin chains, thalassemia, and if it affects both the quality and quantity of the globin chain, the consequence is a thalassemic hemoglobinopathy. The aim of this paper is to present the molecular bases of hemoglobinopathies in Argentina, determined in 862 patients, based on the results of the molecular studies carried out in our laboratory from the analysis of 910 samples. Hb S is the most frequent structural hemoglobinopathy, ß-thalassemia mutations exhibit a pattern similar to the one displayed by Mediterranean basin populations, and a-thalassemia mutations are intrinsically related to the ancestry of those affected. These syndromes exhibit diverse molecular bases: structural hemoglobinopathies and ß-thalassemia are a consequence, mostly of point mutations, whereas in a-thalassemia deletions prevail. Novel mutations (point changes, deletions and duplications) that occurred as isolated events, with recessive or dominant inheritance, were described. Interaction between the hematologist, the geneticist and both the clinical and molecular biology laboratories is necessary to reach an accurate diagnosis of these syndromes and reduce the incidence of severe forms.

Keywords : Hemoglobin; Structural variants; ß-thalassemia; a-thalassemia; Genetics.