Molecular basis for alpha-thalassemia associated with the structural mutant
hemoglobin Suan-Dok (alpha 2 109leu----arg) [published erratum appears in
Blood 1991 Mar 15;77(6):1404]
I Weiss, FE Cash, MB Coleman, A Pressley, JG Adams, T Sanguansermsri, SA Liebhaber and MH Steinberg
Howard Hughes Medical Institute, Department of Human Genetics, University
of Pennsylvania School of Medicine, Philadelphia.
Hemoglobin (Hb) Suan-Dok (alpha 109Arg) is a rare alpha-globin structural
mutation that is linked to an alpha-thalassemia (alpha-thal) determinant.
When inherited in trans to an alpha-thal-1 mutation (-), it results in Hb H
disease associated with low levels (9%) of the Suan- Dok Hb. The nature of
the thalassemic defect associated with the alpha SD mutation has been
investigated by structural and functional studies. Sequence analysis of the
cloned Suan-Dok allele showed a missense mutation (T----G) at codon 109 in
an otherwise normal alpha 2-globin gene. When the alpha 2SD-globin gene was
introduced into mouse erythroleukemia cells, the steady state alpha-globin
messenger RNA (mRNA) level was equivalent to the alpha A-globin gene
control. Although in vitro translation of a synthetic alpha 2SD-globin mRNA
generated levels of alpha globin equivalent to alpha 2A-globin mRNA at
early time points, the ratio of alpha SD to alpha A globin decreased
markedly at later time points. These data suggest that the thalassemic
defect associated with the Suan-Dok mutation results from a significant
instability of the alpha SD globin.
Volume 76,
Issue 12,
pp. 2630-2636,
12/15/1990
Copyright © 1990 by The American Society of Hematology
