[A novel Chinese beta-thalassemia mutation--4bp deletion (AAAC) downstream from the cap site]

During the molecular study of the Chinese beta thalassemia, we encountered a mutation that could not be detected by any of the oligonucleotide probes specific for the known Chinese beta thalassemia mutations. Molecular cloning and DNA sequencing analysis by both DNA chain termination and PCR direct sequencing methods revealed a previously undescribed mutation--deletion of 4bp (-AAAC) at the positions of nucleotide 40 to 43 from the cap site of the beta globin gene. With this new mutation, an additional Dde I recognition site is created and it could be directly detected by analysis of the abnormal restriction fragment. Unlike the other beta thalassemia mutations, this newly described mutant is the first mutation within the 5' untranslated region of beta globin gene as well as any other genes. This unique example will elicit valuable insight in the relationship between the structure and function of the 5' untranslated sequences.