title: Beta-thalassaemia unlinked to the beta-globin gene interacts with sickle-cell trait in a Portuguese family.
abstract: 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.
authors.affiliation: Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa.
authors.forename: P
authors.initials: P
authors.lastname: Pacheco
authors.forename: M J
authors.initials: MJ
authors.lastname: Peres
authors.forename: P
authors.initials: P
authors.lastname: Faustino
authors.forename: C
authors.initials: C
authors.lastname: Pischedda
authors.forename: J
authors.initials: J
authors.lastname: Gonçalves
authors.forename: M
authors.initials: M
authors.lastname: Carvajales-Ramos
authors.forename: T
authors.initials: T
authors.lastname: Seixas
authors.forename: M C
authors.initials: MC
authors.lastname: Martins
authors.forename: P
authors.initials: P
authors.lastname: Moi
authors.forename: J
authors.initials: J
authors.lastname: Lavinha
mesh_terms: D000328:Adult; D001483:Base Sequence; D005260:Female; D005914:Globins / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D011174:Portugal; D017423:Sequence Analysis, RNA; D012805:Sickle Cell Trait / Q000097:blood / Q000150:complications / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000150:complications / Q000235:genetics*
chemical_list: D005914:Globins