|
|
 Previous Article | Table of Contents | Next Article 
Glanzmann's thrombasthenia caused by homozygosity for a splice defect that
leads to deletion of the first coding exon of the glycoprotein IIIa mRNA
S Simsek, H Heyboer, LG de Bruijne-Admiraal, R Goldschmeding, HT Cuijpers and AE von dem Borne
Department of Immunological Haematology, Central Laboratory of the
Netherlands, Red Cross Blood Transfusion Service, Amsterdam.
Glanzmann's thrombasthenia (GT) is the result of the absence or of an
altered and dysfunctional expression on the platelet membrane of the
fibrinogen receptor (glycoprotein [GP] IIb/IIIa complex). Various molecular
genetic mechanisms have been found to be responsible for this inherited
disease. In a patient with a severe type of GT, we have found a splice
variant in the GP IIIa gene that leads to premature chain termination.
Immunoprecipitation experiments, using monoclonal antibodies specific for
GP IIb/IIIa, showed that GP IIb/IIIa was not detectable on the platelet
membrane. Amplification of reversely transcribed platelet GP IIIa mRNA by
the polymerase chain reaction and subsequent sequence analysis showed a
86-bp deletion, which corresponds to exon i of the GP IIIa gene. This
deletion results in a shift of the reading frame leading to eight altered
amino acids followed by a premature termination codon. Analysis of the
corresponding genomic DNA fragments showed three mutations in the exon
i-intron i boundary region of the GP IIIa gene. One of these mutations is a
G-->T transition that eliminates the GT splice donor site in the wild
type. This base pair change creates a restriction site for the enzyme Mse
I. Allele-specific restriction enzyme analysis (ASRA) with Mse I of
amplified genomic DNA of the parents and the proposita showed that both
parents (who are first cousins) are heterozygous, whereas the proposita is
homozygous for the G-->T substitution.
Volume 81,
Issue 8,
pp. 2044-2049,
04/15/1993
Copyright © 1993 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:
|
|
|
|
 
M. Kannan and R. Saxena
Glanzmann's Thrombasthenia: An Overview
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2009;
15(2):
152 - 165.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D Inwald, E G Davies, and N Klein
Demystified ...: Adhesion molecule deficiencies
Mol. Pathol.,
February 1, 2001;
54(1):
1 - 7.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
D. L. Lipscomb, C. Bourne, and M. K. Boudreaux
Two Genetic Defects in {alpha}IIb Are Associated with Type I Glanzmann's Thrombasthenia in a Great Pyrenees Dog: A 14-base Insertion in Exon 13 and a Splicing Defect of Intron 13
Vet. Pathol.,
November 1, 2000;
37(6):
581 - 588.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gonzalez-Manchon, M. Fernandez-Pinel, E. G. Arias-Salgado, M. Ferrer, M.-V. Alvarez, S. Garcia-Munoz, M. S. Ayuso, and R. Parrilla
Molecular Genetic Analysis of a Compound Heterozygote for the Glycoprotein (GP) IIb Gene Associated With Glanzmann's Thrombasthenia: Disruption of the 674-687 Disulfide Bridge in GPIIb Prevents Surface Exposure of GPIIb-IIIa Complexes
Blood,
February 1, 1999;
93(3):
866 - 875.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-C. Morel-Kopp, C. Kaplan, V. Proulle, V. Jallu, C. Melchior, O. Peyruchaud, M.-H. Aurousseau, and N. Kieffer
A Three Amino Acid Deletion in Glycoprotein IIIa Is Responsible for Type I Glanzmann's Thrombasthenia: Importance of Residues Ile325Pro326Gly327 for beta 3 Integrin Subunit Association
Blood,
July 15, 1997;
90(2):
669 - 677.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
