|
|
 Previous Article | Table of Contents | Next Article 
Hereditary spherocytosis with spectrin deficiency due to an unstable
truncated beta spectrin
H Hassoun, JN Vassiliadis, J Murray, SJ Yi, M Hanspal, CA Johnson and J Palek
Department of Biomedical Research, St. Elizabeth's Hospital of Boston, MA,
02135 USA.
Red cell membrane protein analysis by sodium dodecyl sulfate-
polyacrylamide gel electrophoresis (SDS-PAGE) and direct quantitation by
radioimmunoassay or cytofluorometry defines four distinct subsets of
patients with hereditary spherocytosis: Patients with isolated spectrin
deficiency, combined spectrin and ankyrin deficiency, band 3 deficiency,
and protein 4.2 deficiency. In regard to the first group, only one mutation
of beta spectrin has been reported in the literature. We describe a
spectrin variant characterized by a truncated beta chain, and associated
with hereditary spherocytosis and isolated spectrin deficiency. The
clinical phenotype consists of a moderate hemolytic anemia with
spherocytosis and frequent spiculation of the red cells. We present the
biochemical characteristics of this mutant protein and show that it
constitutes only 12% of the total spectrin on the membrane. We show that
the truncation of the protein is the result of a single point mutation at
position +1 (G-->A) of the donor consensus splice site of intron 17
leading to an aberrant beta spectrin transcriptional message lacking exons
16 and 17. To elucidate the basis for the decreased amount of the truncated
protein on the membrane and the overall spectrin deficiency, we provide
evidence that the mutated gene is transcribed but its mRNA is less abundant
than its normal counterpart in reticulocytes; we also show that the mutant
protein is synthesized in decreased amounts in the cytoplasm of erythroid
progenitor cells, and appears to be susceptible to proteolytic degradation.
This mutant spectrin underscores the importance of the regulatory role
played by the beta spectrin molecule in the assembly of alphabeta spectrin
heterodimers on the membrane.
Volume 87,
Issue 6,
pp. 2538-2545,
03/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
T. Yamaguchi, S. Ozaki, T. Shimomura, and S. Terada
Membrane Perturbations of Erythrocyte Ghosts by Spectrin Release
J. Biochem.,
May 1, 2007;
141(5):
747 - 754.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Basseres, D. L. Vicentim, F. F. Costa, S. T.O. Saad, and H. Hassoun
beta -Spectrin Promissao: A Translation Initiation Codon Mutation of the beta -Spectrin Gene (ATG right-arrow GTG) Associated With Hereditary Spherocytosis and Spectrin Deficiency in a Brazilian Family
Blood,
January 1, 1998;
91(1):
368 - 369.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hassoun, J.N. Vassiliadis, J. Murray, P.R. Njolstad, J. J. Rogus, S.K. Ballas, F. Schaffer, P. Jarolim, V. Brabec, and J. Palek
Characterization of the Underlying Molecular Defect in Hereditary Spherocytosis Associated With Spectrin Deficiency
Blood,
July 1, 1997;
90(1):
398 - 406.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
