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Beta-thalassaemia unlinked to the beta-globin gene interacts with sickle-cell trait in a Portuguese family
P Pacheco1, M J Peres, P Faustino
1Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa.
An autosomally transmitted hypochromic microcytic mild anaemia with elevated haemoglobin (Hb) A2 and globin chain imbalance has been observed in a three-generation family of Portuguese origin. Extensive DNA analysis of the beta-globin gene cluster, including the complete sequencing of the beta-globin gene and flanking regions, failed to reveal any genetic alteration. The co-segregation of sickle-cell trait in this family enabled us to postulate a defective erythroid trans-acting factor was playing a role in the down-regulation of both beta A- and beta S-globin genes. Among the transcription factors that could possibly have caused the reported phenotype, NF-E2 is unlikely to be implicated, whereas Nrf1 and Nrf2 cannot be ruled out. Thus, this family carries a novel beta-thalassaemia autosomal determinant unlinked to the beta-globin gene. This observation reinforces the notion of the haemoglobinopathies as single gene disorders under polygenic regulation.
An autosomally transmitted hypochromic microcytic mild anaemia with elevated haemoglobin (Hb) A2 and globin chain imbalance has been observed in a three-generation family of Portuguese origin. Extensive DNA analysis of the beta-globin gene cluster, including the complete sequencing of the beta-globin gene and flanking regions, failed to reveal any genetic alteration. The co-segregation of sickle-cell trait in this family enabled us to postulate a defective erythroid trans-acting factor was playing a role in the down-regulation of both beta A- and beta S-globin genes. Among the transcription factors that could possibly have caused the reported phenotype, NF-E2 is unlikely to be implicated, whereas Nrf1 and Nrf2 cannot be ruled out. Thus, this family carries a novel beta-thalassaemia autosomal determinant unlinked to the beta-globin gene. This observation reinforces the notion of the haemoglobinopathies as single gene disorders under polygenic regulation.