Distal CCAAT box deletion in the A globin gene of two black adolescents with elevated fetal A globin

Abstract
Point mutations in G.gamma. and A.gamma. globin gene promoters are associated with increased production of G.gamma. and A.gamma. globin, respectively. To determine whether an upstream promoter mutation could account for elevated A.gamma. in a Black adolescent with A.gamma.-.beta.+4-HPFH and sickle cell trait, we cloned the 13 kb BglII fragment containing both .gamma. genes into phage lambda vector EMBL3. For one clone, the A.gamma. upstream promoter showed no hybridization to a 19 bp oligonucleotide whose sequence centered at -117. A.gamma. promoter sequence data for this mutant clone revealed a 13 bp deletion which eliminated the A.gamma. distal CCAAT box. Amplified A.gamma. genomic DNA of this and a similar case showed hybridization to both deletion-mutant and normal oligonucleotide probes. We propose that this 13 bp deletion removes part of the binding site for a repressor protein which is abundant in adult erythroid cells.