|
|
 Previous Article | Table of Contents | Next Article 
Factor IX New London: substitution of proline for glutamine at position 50
causes severe hemophilia B
JN Lozier, DM Monroe, S Stanfield-Oakley, SW Lin, KJ Smith, HR Roberts and KA High
Department of Medicine, University of North Carolina, Chapel Hill 27599-
7035.
We describe a novel point mutation in the fourth exon of human factor IX
(encoding the first EGF-like domain) in which cytosine is substituted for
adenosine at position 10,401, resulting in the substitution of proline for
glutamine at position 50 in the polypeptide chain. Sequence analysis of all
eight exons, all exon-intron junctions, 160 base pairs (bp) of DNA 5' to
the proposed translation start site, and 60 bp 3' to the translation
termination site shows no other difference from the normal factor IX gene,
with the exception of a previously described benign polymorphism at
position 148 in the protein (Ala----Thr). The affected subject has severe
hemophilia B with no detectable factor IX activity despite normal factor IX
antigen levels. We purified the abnormal factor IX by immunoaffinity
chromatography and demonstrated that its activation by factor Xla is
markedly delayed compared with normal factor lX. Once activated, the
abnormal factor lX binds antithrombin III in a 1:1 molar ratio, and the
activated protein demonstrates catalytic activity, suggesting an intact
active site. The mutation creates a new Bst Yl restriction endonuclease
cleavage site. Restriction with Bst Yl shows the mutation in maternal DNA
and offers the possibility of direct carrier status analysis and prenatal
diagnosis in kindreds with this mutation. We designate this new mutation
factor lXNew London. This is the only reported mutation in the first
EGF-like domain that causes severe hemophilia B.
Volume 75,
Issue 5,
pp. 1097-1104,
03/01/1990
Copyright © 1990 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:
|
|
|
|
 
J. P. Sheehan and E. N. Walke
Depolymerized holothurian glycosaminoglycan and heparin inhibit the intrinsic tenase complex by a common antithrombin-independent mechanism
Blood,
May 15, 2006;
107(10):
3876 - 3882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Aktimur, M. A. Gabriel, D. Gailani, and J. R. Toomey
The Factor IX gamma -Carboxyglutamic Acid (Gla) Domain Is Involved in Interactions between Factor IX and Factor XIa
J. Biol. Chem.,
February 28, 2003;
278(10):
7981 - 7987.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Sichler, E. Kopetzki, R. Huber, W. Bode, K.-P. Hopfner, and H. Brandstetter
Physiological fIXa Activation Involves a Cooperative Conformational Rearrangement of the 99-Loop
J. Biol. Chem.,
January 31, 2003;
278(6):
4121 - 4126.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E. M. Persson, B. O. Villoutreix, A.-M. Thamlitz, K. E. Knobe, and J. Stenflo
The N-terminal Epidermal Growth Factor-like Domain of Coagulation Factor IX. PROBING ITS FUNCTIONS IN THE ACTIVATION OF FACTOR IX AND FACTOR X WITH A MONOCLONAL ANTIBODY
J. Biol. Chem.,
September 13, 2002;
277(38):
35616 - 35624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Hertzberg, S. L. Facey, and P. J. Hogg
An Arg/Ser Substitution in the Second Epidermal Growth Factor-Like Module of Factor IX Introduces an O-Linked Carbohydrate and Markedly Impairs Activation by Factor XIa and Factor VIIa/Tissue Factor and Catalytic Efficiency of Factor IXa
Blood,
July 1, 1999;
94(1):
156 - 163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chang, J. Jin, P. Lollar, W. Bode, H. Brandstetter, N. Hamaguchi, D. L. Straight, and D. W. Stafford
Changing Residue 338 in Human Factor IX from Arginine to Alanine Causes an Increase in Catalytic Activity
J. Biol. Chem.,
May 15, 1998;
273(20):
12089 - 12094.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Larson, S. A. Stanfield-Oakley, W. J. VanDusen, C. K. Kasper, K. J. Smith, D. M. Monroe, and K. A. High
Structural Integrity of the [IMAGE]-Carboxyglutamic Acid Domain of Human Blood Coagulation Factor IXa Is Required for Its Binding to Cofactor VIIIa
J. Biol. Chem.,
February 16, 1996;
271(7):
3869 - 3876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. H. Wilkinson, F. S. London, and P. N. Walsh
Residues 88-109 of Factor IXa Are Important for Assembly of the Factor X Activating Complex
J. Biol. Chem.,
February 15, 2002;
277(8):
5725 - 5733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
