|
|
 Previous Article | Table of Contents | Next Article 
The first mutation identified in the thrombomodulin gene in a 45-year- old
man presenting with thromboembolic disease
AK Ohlin and RA Marlar
Department of Clinical Chemistry, University Hospital, Lund, Sweden.
Thrombomodulin (TM) is the anticoagulant endothelial cell membrane- bound
protein cofactor in the thrombin-mediated activation of protein C (PC). It
has been clearly demonstrated that the anticoagulant and profibrinolytic
functions of the PC system are important for the prevention of a
thromboembolic disease. Patients with PC, protein S, or PC "'cofactor"'
deficiency and/or dysfunction develop thromboembolic diseases. However, the
molecular abnormality in at least 20% to 30% of thrombophilic patients
cannot be identified by hitherto recognized defects. A putative pathologic
lesion in the TM gene could be one of several candidates for these
prothrombotic mutations. A directed search strategy for deletions,
insertions, or point mutations in the TM gene has not been performed.
Therefore, in the present study, we have analyzed the entire TM gene,
including the promoter region, by polymerase chain reaction-single-strand
conformation polymorphism (PCR- SSCP) in normal healthy volunteers and in
patients presenting with a thromboembolic disease. We have identified a
patient with a thromboembolic disease and a TM point mutation. In a
45-year-old Hispanic man with a documented pulmonary embolism, PCR-SSCP
showed an aberrant band pattern and subsequent DNA sequence analysis showed
a heterozygous substitution for G1456 to T. This substitution predicts an
Asp468 to a Tyr change in the amino acid sequence that is located between
the transmembrane domain and the sixth epidermal growth factor- like
domain. The Asp468 to Tyr change would probably lead to significant
structural changes not allowing the expression of the TM protein or to a
conformational change that is not functional.
Volume 85,
Issue 2,
pp. 330-336,
01/15/1995
Copyright © 1995 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:
|
|
|
|
 
G. Kunz, A.-K. Ohlin, A. Adami, B. Zoller, P. Svensson, and D. A. Lane
Naturally occurring mutations in the thrombomodulin gene leading to impaired expression and function
Blood,
May 15, 2002;
99(10):
3646 - 3653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Weiler, V. Lindner, B. Kerlin, B. H. Isermann, S. B. Hendrickson, B. C. Cooley, D. A. Meh, M. W. Mosesson, N. W. Shworak, M. J. Post, et al.
Characterization of a Mouse Model for Thrombomodulin Deficiency
Arterioscler. Thromb. Vasc. Biol.,
September 1, 2001;
21(9):
1531 - 1537.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Schatteman, F. Goossens, J. Leurs, R. Verkerk, S. Scharpe, J. J. Michiels, and D. Hendriks
arboxypeptidase U at the Interface Between Coagulation and Fibrinolysis
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2001;
7(2):
93 - 101.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. K. Wu, N. Aleksic, C. Ahn, E. Boerwinkle, A. R. Folsom, and H. Juneja
Thrombomodulin Ala455Val Polymorphism and Risk of Coronary Heart Disease
Circulation,
March 13, 2001;
103(10):
1386 - 1389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Waugh, J. Li-Hawkins, E. Yuksel, M. D. Kuo, P. N. Cifra, P. R. Hilfiker, R. Geske, M. Chawla, J. Thomas, S. M. Shenaq, et al.
Thrombomodulin Overexpression to Limit Neointima Formation
Circulation,
July 18, 2000;
102(3):
332 - 337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Lane and P. J. Grant
Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease
Blood,
March 1, 2000;
95(5):
1517 - 1532.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Simmonds and D. A. Lane
Structural and Functional Implications of the Intron/Exon Organization of the Human Endothelial Cell Protein C/Activated Protein C Receptor (EPCR) Gene: Comparison With the Structure of CD1/Major Histocompatibility Complex alpha 1 and alpha 2 Domains
Blood,
July 15, 1999;
94(2):
632 - 641.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Salomon, D. M. Steinberg, A. Zivelin, S. Gitel, R. Dardik, N. Rosenberg, S. Berliner, A. Inbal, A. Many, A. Lubetsky, et al.
Single and Combined Prothrombotic Factors in Patients With Idiopathic Venous Thromboembolism : Prevalence and Risk Assessment
Arterioscler. Thromb. Vasc. Biol.,
March 1, 1999;
19(3):
511 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Waugh, E. Yuksel, J. Li, M. D. Kuo, M. Kattash, R. Saxena, R. Geske, S. N. Thung, S. M. Shenaq, and S. L. C. Woo
Local Overexpression of Thrombomodulin for In Vivo Prevention of Arterial Thrombosis in a Rabbit Model
Circ. Res.,
January 22, 1999;
84(1):
84 - 92.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Healy, W. W. Hancock, P. D. Christie, H. B. Rayburn, and R. D. Rosenberg
Intravascular Coagulation Activation in a Murine Model of Thrombomodulin Deficiency: Effects of Lesion Size, Age, and Hypoxia on Fibrin Deposition
Blood,
December 1, 1998;
92(11):
4188 - 4197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Laffan
Genetics and pulmonary medicine bullet 4: Pulmonary embolism
Thorax,
August 1, 1998;
53(8):
698 - 702.
[Full Text]
|
|
|
|
|
|
|
H. Ireland, G. Kunz, K. Kyriakoulis, P. J. Stubbs, and D. A. Lane
Thrombomodulin Gene Mutations Associated With Myocardial Infarction
Circulation,
July 1, 1997;
96(1):
15 - 18.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Kalafatis and K. G. Mann
Factor VLeiden and Thrombophilia
Arterioscler. Thromb. Vasc. Biol.,
April 1, 1997;
17(4):
620 - 627.
[Full Text]
|
|
|
|
|
|
|
C. van `t Veer, N. J. Golden, M. Kalafatis, and K. G. Mann
Inhibitory Mechanism of the Protein C Pathway on Tissue Factor-induced Thrombin Generation. SYNERGISTIC EFFECT IN COMBINATION WITH TISSUE FACTOR PATHWAY INHIBITOR
J. Biol. Chem.,
March 21, 1997;
272(12):
7983 - 7994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Cadroy, A. Diquelou, D. Dupouy, J.P. Bossavy, K.S. Sakariassen, P. Sie, and B. Boneu
The Thrombomodulin/Protein C/Protein S Anticoagulant Pathway Modulates the Thrombogenic Properties of the Normal Resting and Stimulated Endothelium
Arterioscler. Thromb. Vasc. Biol.,
March 1, 1997;
17(3):
520 - 527.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
E. M. Faioni, G. Merati, F. Peyvandi, P. M. Bettini, and P. M. Mannucci
The G1456 to T Mutation in the Thrombomodulin Gene Is Not Frequent in Patients With Venous Thrombosis
Blood,
February 15, 1997;
89(4):
1467 - 1467.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Conway, S. Pollefeyt, D. Collen, and M. Steiner-Mosonyi
The Amino Terminal Lectin-Like Domain of Thrombomodulin Is Required for Constitutive Endocytosis
Blood,
January 15, 1997;
89(2):
652 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Weisel, C. Nagaswami, T. A. Young, and D. R. Light
The Shape of Thrombomodulin and Interactions with Thrombin as Determined by Electron Microscopy
J. Biol. Chem.,
December 6, 1996;
271(49):
31485 - 31490.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
