Beta-thalassaemia unlinked to the beta-globin gene interacts with sickle-cell trait in a Portuguese family.
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.
Pacheco
P
P
Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa.
Peres
M J
MJ
Faustino
P
P
Pischedda
C
C
Gonçalves
J
J
Carvajales-Ramos
M
M
Seixas
T
T
Martins
M C
MC
Moi
P
P
Lavinha
J
J
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*
D005914:Globins