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(Reference retrieved automatically from SciELO through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Investigating alpha-globin structural variants: a retrospective review of 135,000 Brazilian individuals

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Author(s):
Elza Miyuki Kimura ; Denise Madureira Oliveira ; Susan Elisabeth Jorge ; Daniela Maria Ribeiro ; Tânia Regina Zaccariotto ; Magnun Nueldo Nunes Santos ; Vanessa Almeida ; Dulcinéia Martins Albuquerque ; Fernando Ferreira Costa ; Maria de Fátima Sonati
Total Authors: 10
Document type: Journal article
Source: Revista Brasileira de Hematologia e Hemoterapia; v. 37, n. 2, p. -, Abr. 2015.
Abstract

Background: Brazil has a multiethnic population with a high diversity of hemoglobinopathies. While screenings for beta-globin mutations are far more common, alterations affecting alpha-globin genes are usually more silent and less well known. The aim of this study was to describe the results of a screening program for alpha-globin gene mutations in a representative sample of the Southeastern Brazilian population. Methods: A total of 135,000 individuals, including patients with clinical suspicion of hemoglobinopathies and their family members, randomly chosen individuals submitted to blood tests and blood donors who were abnormal hemoglobin carriers were analyzed. The variants were screened by alkaline and acid electrophoreses, isoelectric focusing and cation-exchange high performance liquid chromatography (HPLC) and the abnormal chains were investigated by reverse-phase high performance liquid chromatography (RP-HPLC). Mutations were identified by molecular analyses, and the oxygen affinity, heme-heme cooperativity and Bohr effect of the variants were evaluated by functional tests. Results: Four new and 22 rare variants were detected in 98 families. Some of these variants were found in co-inheritance with other hemoglobinopathies. Of the rare hemoglobins, Hasharon, Stanleyville II and J-Rovigo were the most common, the first two being S-like and associated with alpha-thalassemia. Conclusion: The variability of alpha-globin alterations reflects the high degree of racial miscegenation and an intense internal migratory flow between different Brazilian regions. This diversity highlights the importance of programs for diagnosing hemoglobinopathies and preventing combinations that may lead to important clinical manifestations in multiethnic populations. (AU)

FAPESP's process: 10/00560-8 - Caracterization of deletional alpha-thalasssemic genotypes by MLPA
Grantee:Maria de Fatima Sonati
Support type: Regular Research Grants
FAPESP's process: 08/57441-0 - Clinical, cellular and molecular alterations in hemoglobinopathies and other hereditary hemolytic anemias
Grantee:Fernando Ferreira Costa
Support type: Research Projects - Thematic Grants