Laotian (delta beta) degree-thalassemia: molecular characterization of a
novel deletion associated with increased production of fetal hemoglobin
JW Zhang, G Stamatoyannopoulos and NP Anagnou
Department of Medicine, University of Washington, Seattle 98195.
We have identified and molecularly characterized a novel deletion in the
beta-globin gene cluster that increases fetal hemoglobin (HbF) synthesis in
a 24-year-old Laotian man who is heterozygous for this mutation. The
patient is asymptomatic with a mild anemia, hypochromia, and microcytosis
(Ht = 39%, MCH = 22.8 pg, MCV = 71 fl), normal levels of HbA2 (3.0%) and
11.5% HbF (G gamma A gamma ratio 60 to 40), with heterocellular
distribution (52% F cells). Extensive restriction endonuclease mapping
defined the 5' breakpoint within the IVS II of the delta-globin gene,
between positions 775 to 781 very similar to the 5' breakpoint of the
Sicilian delta beta-thalassemia. However, the 3' breakpoint was localized
between two Pst I sites 4.7 kb 3' of the beta- globin gene, thus ending
about 0.7 kb upstream from the 3' breakpoint of the Sicilian delta
beta-thalassemia. This results in a 12.5 kb deletion of DNA. It is of
interest that the 5' breakpoint of the deletion residues within an AT-rich
region which has been proposed as a specific recognition signal for
recombination events, while the 3' breakpoint lies within a cluster of L1
repetitive sequences (formerly known as Kpn I family repeats). The presence
of the 3' breakpoints of several other deletions within this region of L1
repeats also suggests that such sequences might serve as hot spots for
recombination and eventually lead to thalassemia deletions. The similarity
of the 5' and 3' breakpoints of these delta beta-thalassemias underscores
the putative regulatory role of the deleted and juxtaposed sequences on the
expression of the gamma-globin genes in adult life.
Volume 72,
Issue 3,
pp. 983-988,
09/01/1988
Copyright © 1988 by The American Society of Hematology
