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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Revista Brasileira de Hematologia e Hemoterapia; v. 37, n. 2, p. 103-108, 2015-04-00.

Resumo

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)

• Processo FAPESP: 08/57441-0 - Alterações clínicas, celulares e moleculares nas hemoglobinopatias e em outras anemias hemolíticas hereditárias
• Beneficiário: Fernando Ferreira Costa
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/00560-8 - CARACTERIZAÇÃO DE GENÓTIPOS DA TALASSEMIA ALFA DELECIONAL POR MLPA(Multiplex Ligation-dependent Probe Amplification)
• Beneficiário: Maria de Fatima Sonati
• Modalidade de apoio: Auxílio à Pesquisa - Regular