Contribution to the study of molecular defects of hemoglobin in the Brazilian population

ABSTRACT

The hemoglobinopathies belong to a diverse group of inherited disorders characterized by the reduced synthesis of one or more globin chains (thalassemia) or the synthesisof a structurally abnormal hemoglobin (Hb). Approximately 900 different hemoglobin variants characterized by mutations involving alpha, beta, gamma, and delta globin chains have been described worldwide. In Brazil, the high degree of ethnic admixture among native Americans and African and European descendants has produced elevated frequencies of Hb alterations. The aim of the present study was to characterize globin chain mutants based on classical laboratory tests and molecular analyses to supply detailed informationabout the Hb diseases to health professionals and to contribute to the knowledge of abnormal hemoglobins in Brazil. A total of 242 samples were submitted to classical tests selected for hemoglobinopathies, and molecular screening was carried out by PCR-based techniques that included allele-specific PCR, multiplex PCR, restriction enzyme analysis PCR, and direct sequencing. After conducting the classical tests, the samples were divided into five groups in accordance with the mutant chain. The groups with alpha and beta globin chain mutants were the most frequent, with 81 samples each. Another group with a large number of samples was that of unidentified mutants, with 56 samples. The delta and fusing delta/beta globin chain groups had fewer numbers of samples, respectively, 13 and 11. The most frequent electrophoretic profile was the Hb S-like, followed by fast variants. Some sample of the beta globin chain group could only be identified after sequencing, such as the samples Hb D-Los Angeles, Hb Korle-Bu, Hb K-Woolwich, Hb E, Hb Deer Lodge, Hb Osu-Christiansborg, and Hb Ohio. It was possible to detect a previously undescribed variant in four individuals of this sampling, who were not related and from different locations. For the alpha globin chain mutants, sequencing of the...