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β‐Thalassaemia unlinked to the β‐globin gene interacts with sickle‐cell trait in a Portuguese family
Author(s) -
Pacheco P.,
Peres M. J.,
Faustino P.,
Pischedda C.,
Gonclalves J.,
CarvajalesRamos M.,
Seixas T.,
Martins M. C.,
Moi P.,
Lavinha J.
Publication year - 1995
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1995.tb05249.x
Subject(s) - genetics , biology , gene , globin , gene cluster , phenotype , gene family , microbiology and biotechnology , gene expression
Summary An autosomally transmitted hypochromic microcytic mild anaemia with elevated haemoglobin (Hb) A 2 and globin chain imbalance has been observed in a three‐generation family of Portuguese origin. Extensive DNA analysis of the β‐globin gene cluster, including the complete sequencing of the,β‐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 β A ‐ and β 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 β‐thalassaemia autosomal determinant unlinked to the β‐globin gene. This observation reinforces the notion of the haemoglobinopathies as single gene disorders under polygenic regulation.