α-Thalassaemia as a result of a novel splice donor site mutation of the α1-globin gene

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 alpha(1)-globin gene (alpha(1)IVS I-1). The mutation was found in combination with the South-East Asian alpha(0)-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 alpha(1)-globin gene. No normally spliced alpha(1)mRNA was detected. The abnormally spliced mRNA product from the al-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha(0)-thalassaemia.