The ß-globin gene on the Chinese dß-thalassemia chromosome carries a promoter mutation

A new type of dß-thalassemia characterized by decreased expression of the ß-globin gene and increased expression of both (G)? and (A)? globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant ß-globin gene from this dß-thalassemia chromosome. An A to G transversion is identified in the 'ATA' sequence of the promoter region that leads to decreased expression of the ß-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese ß-thalassemia genes where it is present on chromosomes of the same haplotype as that of the dß-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the dß-thalassemia phenotype.