A new mutation of IVS-1 of the human β globin gene causing β thalassemia due to abnormal splicing

A G to T transversion at the fifth nucleotide of the first intervening sequence (IVS-1) of the β-globin gene has been identified in cloned β-thalassemia genes of two unrelated individuals, one of Mediterranean and the other of Anglo Saxon ancestry. In each patient the mutation was present in a different β globin gene framework, defined by intragenic restriction site polymorphism, thereby suggesting the occurrence of independent mutations. The study of the RNA products of one of these cloned genes, after transfer and transient expression in HeLa cells, showed partial inactivation of the normal donor splice site of IVS-1 and activation of two major and one minor cryptic splice sites. Only one of the two major cryptic sites was utilized in a cell-free splicing extract. The effects of this mutation on messenger RNA (mRNA) splicing are similar to that of another β thalassemia gene with a G to C transition at the same position.