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

We describe the characterization of an α⁺-thalassaemia determinant as a result of a transition of G→A of the donor splice consensus site sequence of the first intron of the α₁-globin gene (α₁IVS I-1). The mutation was found in combination with the South-East Asian α⁰-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 α₁-globin gene. No normally spliced α₁mRNA was detected. The abnormally spliced mRNA product from the α₁-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type α⁰-thalassaemia.