Dutch β°‐thalassaemia: a 10 kilobase DNA deletion associated with significant γ‐chain production

Abstract

A unique beta 0-thalassaemia in a Dutch family results in fetal haemoglobin expression comparable to that of delta 0 beta 0-thalassaemia. Haemoglobin analysis and restriction endonuclease mapping studies of DNA suggest that the beta-globin gene is entirely deleted, but that the delta-globin gene is intact. The 5' break point of the deletion is 3-4 kilobases 3' to the delta-globin gene, while the 3' break point is 6-7 kilobases 3' to the beta-globin gene (relative to the normal DNA restriction map). The result is a approximately 10 kilobase deletion of DNA whose 3' end point may lie very close to that for one delta 0 beta 0-thalassaemia, within a cluster of Kpn I-family repetitive sequences. The Dutch beta 0-thalassaemia deletion is thus the shortest one which, in the absence of additional chromosomal rearrangements, results in enhancement of gamma-chain synthesis above that seen for haemoglobin Lepore. These data support the hypothesis that the region of DNA 3' to the beta-globin gene may be important to the developmental regulation of fetal gamma versus adult beta chain production.