alpha-thalassaemia as a result of a novel splice donor site mutation of the alpha1-globin gene

Abstract

We describe the characterization of an alpha+-thalassaemia determinant as a result of a transition of G-->A of the donor splice consensus site sequence of the first intron of the alpha1-globin gene (alpha1IVS I-1). The mutation was found in combination with the South-East Asian alpha0-thalassaemia deletion in an haemoglobin (Hb)H patient and her sister, both of Thai origin. Sequencing of the abnormally spliced mRNA product revealed the presence of a cryptic splice site in exon 1 of the alpha1-globin gene. No normally spliced alpha1mRNA was detected. The abnormally spliced mRNA product from the alpha1-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha0-thalassaemia.