A substitution of cytosine for thymine in codon 110 of the human beta-globin gene is a novel cause of beta-thalassemia phenotypes.

We have described a novel human globin gene mutation that produced in a Japanese family the beta-thalassemia phenotype through a post-translational mechanism. Substitution of proline for leucine at position 110 in the G-helix of the beta-globin chain greatly reduced the molecular stability of the beta-globin subunit, leading to total destruction of the variant globin chains by proteolysis and hence to the beta-thalassemia phenotype. The mutation could be identified after MspI digestion. This detection of the mutation on the gene level is valuable for diagnostic purposes.