alpha-Thalassaemia as a result of a novel splice donor site mutation of the alpha(1)-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 seq uence of the first intron of the alpha(1)-globin gene (alpha(1)IVS I-1). Th e mutation was found in combination with the South-East Asian alpha(0)-thal assaemia deletion in an haemoglobin (Hb)H patient and her sister, both of T hai 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 pr oduct from the al-gene carrying the mutation does not lead to functional pr otein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha(0)-thalassaemia.