Sardinian delta beta zero-thalassemia: a further example of a C to T
substitution at position -196 of the A gamma globin gene promoter
S Ottolenghi, B Giglioni, A Pulazzini, P Comi, C Camaschella, A Serra, A Guerrasio and G Saglio
Selective overexpression (50- to 100-fold) in adult erythroid cells of
either G gamma or A gamma fetal globin gene is observed in hereditary
conditions known as delta beta zero-thalassemia and hereditary persistence
of fetal hemoglobin (HPFH). Recently, a C----T change at position -196 of
an overexpressed A gamma globin gene from an Italian HPFH was hypothesized,
on the basis of indirect evidence, to represent the cause of the functional
defect. We now show that the same mutation is present in a different
overexpressed A gamma-globin gene from a Sardinian patient with a different
syndrome (delta beta zero- thalassemia). The Sardinian A gamma globin gene
differs from both the HPFH and the normal A gamma globin gene at nucleotide
1,560 in the noncoding portion of the third exon, where an A is deleted. In
addition, the mutant -196 A gamma-globin gene is linked to a normal beta
globin gene in HPFH, and to a beta-thalassemic gene (beta 39CAG---- TAG) in
delta beta zero-thalassemia. These data strengthen the suggestion that -196
mutation is causally linked to the abnormal phenotype and raise the
question of whether the same or multiple mutational events are responsible
for the appearance of the -196 mutation in different syndromes.
Volume 69,
Issue 4,
pp. 1058-1061,
04/01/1987
Copyright © 1987 by The American Society of Hematology
