Beta-thalassaemia unlinked to the beta-globin gene interacts with sickle-cell trait in a Portuguese family

• Published in: British journal of haematology Vol. 91; no. 1; p. 85
• Main Authors: Pacheco, P, Peres, M J, Faustino, P, Pischedda, C, Gonçalves, J, Carvajales-Ramos, M, Seixas, T, Martins, M C, Moi, P, Lavinha, J
• Format: Journal Article
• Language: English
• Published: England 01.09.1995
• Subjects: Adult; Base Sequence; beta-Thalassemia - blood; beta-Thalassemia - complications; beta-Thalassemia - genetics; Female; Globins - genetics; Humans; Male; Molecular Sequence Data; Pedigree; Portugal; Sequence Analysis, RNA; Sickle Cell Trait - blood; Sickle Cell Trait - complications; Sickle Cell Trait - genetics; Portugal
• ISSN: 0007-1048
• DOI: 10.1111/j.1365-2141.1995.tb05249.x

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.