|
|
 Previous Article | Table of Contents | Next Article 
Glanzmann thrombasthenia caused by an 11.2-kb deletion in the glycoprotein
IIIa (beta3) is a second mutation in Iraqi Jews that stemmed from a
distinct founder
N Rosenberg, R Yatuv, Y Orion, A Zivelin, R Dardik, H Peretz and U Seligsohn
Department of Hematology, Sheba Medical Center, Tel-Hashomer and Sackler
School of Medicine, Tel-Aviv University, Israel.
Glanzmann thrombasthenia (GT) is a rare bleeding disorder resulting from
mutations in either glycoprotein (GP) IIb or GPIIIa genes. The disease is
relatively frequent in highly inbred populations such as Iraqi Jews. The
molecular basis of GT in 6 unrelated Iraqi-Jewish patients was previously
identified as an 11-bp deletion in exon 12 of the GPIIIa gene. We now
describe a second mutation found in 3 unrelated Iraqi-Jewish families that
consists of an 11.2-kb deletion between an Alu repeat in intron 9 and exon
13 of the GPIIIa gene. The mutant DNA is transcribed into mRNA in which
exons 10 through 13 are absent. Splicing of exon 9 directly to exon 14
leads to a shift in the reading frame resulting in a stop codon. The
predicted protein is truncated in the middle of the third cysteine-rich
domain before the transmembrane domain. Simple DNA-based methods were
devised for identification of both mutations in Iraqi Jews for the purpose
of carrier detection and prenatal diagnosis enabling prevention of GT. A
survey of the general Iraqi-Jewish population for the first 11-bp deletion
and the second 11.2-kb deletion disclosed that the allele frequency of the
first mutation was 0.0043, whereas none of 700 individuals examined bore
the second mutation (allele frequency <0.0007). Among 40 GT patients of
Iraqi-Jewish origin 31 were homozygous for the first mutation, 4 were
compound heterozygotes for the first and second mutations, and 2 were
homozygous for the second mutation. Haplotype analyses using 4 polymorphic
markers in the GPIIIa gene showed that each mutation originated in a
distinct founder.
Volume 89,
Issue 10,
pp. 3654-3662,
05/15/1997
Copyright © 1997 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]
|
|
|
|
|
|
|
R. Yatuv, N. Rosenberg, A. Zivelin, H. Peretz, R. Dardik, L. Trakhtenbrot, and U. Seligsohn
Identification of a region in glycoprotein IIIa involved in subunit association with glycoprotein IIb: further lessons from Iraqi-Jewish Glanzmann thrombasthenia
Blood,
August 15, 2001;
98(4):
1063 - 1069.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Ward, A. S. Kestin, and P. J. Newman
A Leu262Pro mutation in the integrin beta 3 subunit results in an alpha IIb-beta 3 complex that binds fibrin but not fibrinogen
Blood,
July 1, 2000;
96(1):
161 - 169.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.A. Thornton, M. Poncz, M. Korostishevsky, E. Yakobson, S. Usher, U. Seligsohn, and H. Peretz
The Human Platelet alpha IIb Gene Is Not Closely Linked to Its Integrin Partner beta 3
Blood,
September 15, 1999;
94(6):
2039 - 2047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Ody, P. Vaigot, P. Quere, B. A. Imhof, and C. Corbel
Glycoprotein IIb-IIIa Is Expressed on Avian Multilineage Hematopoietic Progenitor Cells
Blood,
May 1, 1999;
93(9):
2898 - 2906.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Shpilberg, I. Rabi, K. Schiller, R. Walden, D. Harats, K.S. Tyrrell, B. Coller, and U. Seligsohn
Patients With Glanzmann Thrombasthenia Lacking Platelet Glycoprotein {alpha}IIb{beta}3 (GPIIb/IIIa) and {alpha}v{beta}3 Receptors Are Not Protected From Atherosclerosis
Circulation,
March 5, 2002;
105(9):
1044 - 1048.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
