A novel basis for dß-thalassemia in a Chinese family

We have studied a Chinese family in which ß-thalassemia and dß-thalassemia were found in simple and compound heterozygous states. The dß-thalassemia heterozygote (the mother) had 22.3% hemoglobin F, of which 40% was (G)? and 60% (A)?; globin chain studies showed an a/ß + ? ratio of 1.36. The compound heterozygote for dß-thalassemia and ß-thalassemia (the child) had the clinical picture of thalassemia intermedia and an a/ß + ? ratio of 4.44. Gene mapping studies were performed using DNA from the affected child. Seventy kilobases of DNA in the ß-globin gene cluster starting upstream from the e-globin gene and ending downstream from the ß-globin gene were mapped, and no detectable deletions or rearrangements were detected. In addition, heterozygosity was detected at multiple polymorphic restriction sites in and 3' to the ß-globin gene, which excludes the possibility of a deletion of the entire ß-globin gene cluster. This is the first example of a nondeletion dß-thalassemia associated with increased expression of both (G)? and (A)? genes.