A novel deletion of approximately 27 kb including the beta-globin gene and
the locus control region 3'HS-1 regulatory sequence: beta zero- thalassemia
or hereditary persistence of fetal hemoglobin?
AJ Dimovski, V Divoky, AD Adekile, E Baysal, JB Wilson, JF Prior, JL Raven and TH Huisman
Laboratory of Protein Chemistry, Medical College of Georgia, Augusta
30912-2100.
A novel deletion of approximately 27 kb with the 5' breakpoint 1.5 to 2.2
kb upstream of the beta-globin gene, and the 3' breakpoint approximately 24
kb downstream of the beta-globin gene, has been found in five members of
two families from Southeast Asia (Vietnam and Cambodia). Six members of
another family from China, previously reported from our laboratory, have
also been shown to carry this deletion. The patients presented with mild
hypochromia and microcytosis, a hemoglobin (Hb) A2 level of approximately
4.0%, and a markedly increased, heterocellularly distributed, Hb F level
(14.0 to 26.0%). In vitro globin-chain synthesis showed a mild imbalance
with appreciable gamma-chain compensation (alpha/beta + gamma ratio of
1.46). The 3' end of this deletion includes the 3'HS-1, and we hypothesize
that removal of this region results in the loss of its gamma-globin
gene-silencing effect, which causes a markedly elevated Hb F level with a
modest increase in Hb A2 levels, unlike the situation in other deletional
beta zero-thalassemias. The possible influence of particular sequence
variations in the locus control region 5'HS-2 and the G gamma promoter,
present on the chromosome with this deletion, on the overall gamma-globin
gene should also be considered.
Volume 83,
Issue 3,
pp. 822-827,
02/01/1994
Copyright © 1994 by The American Society of Hematology
