Nucleic Acids Research, 1988, Vol. 16, No. 13 6057-6066
© 1988
Articles |
Molecular characterization of a novel form of (A
ß)°-thalassemia, deletion with a 3' breakpoint close to those of HPFH-3 and HPFH-4: insights for a common regulatory mechanism
Divisions of Medical Genetics and Hematology, Department of Medicine, University of Washington Seattle, WA 98195, USA 1Clinical Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health Bethesda, MD 20205, USA
*To whom correspondence should be addressed
Received December 7, 1987. Revised May 27, 1988. Accepted May 27, 1988.
We have molecularly characterized a novel (A
ß)°-thalassemia associated with increased synthesis of HbF in three members of a German family. The levels of HbF in the peripheral blood red cells of the heterozygotes ranged between 9.9% and 12.5% with a heterocellular distribution in the red cells, as detected by immunofluorescence. The mutation resulted from a deletion starting about 1.5 to 1.9 kb from the 3' end of the G-gene and ending 27±0.5 kb 3' to the ß-globin gene. Thus, the total deletion is 52±0.5 kb. Its 5' breakpoint is similar to that of the previously described (Aß)°-thalassemias, while the location of the 3' breakpoint is placed very close to the 3' breakpoints of HPFH-4 and HPFH-3 deletions. The proximity of the 3' breakpoint of the German (Aß)°-thalassemia to those of HPFH-3 and HPFH-4 deletions raises the possibility that a common mechanism, such as the juxtaposition of an enhancer, might underlie the activation of the -globin genes in these three mutants.