|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2253-2260
Molecular Analysis of the ERGIC-53 Gene in 35 Families With
Combined Factor V-Factor VIII Deficiency
M. Neerman-Arbez,
K.M. Johnson,
M.A. Morris,
J.H. McVey,
F. Peyvandi,
W.C. Nichols,
D. Ginsburg,
C. Rossier,
S.E. Antonarakis, and
E.G.D. Tuddenham
From the Department of Genetics and Microbiology, Division of Medical
Genetics, University of Geneva Medical School; Haemostasis Research
Group, MRC Clinical Sciences Centre, Imperial College School of
Medicine, London, UK; the Division of Medical Genetics, Cantonal
Hospital of Geneva, Switzerland; Bonomi Haemophilia and Thrombosis
Center, IRCCS Maggiore Hospital and University of Milano, Italy; and
the Department of Medicine, Howard Hughes Medical Institute, University
of Michigan, Ann Arbor, MI.
Combined factor V-factor VIII deficiency (F5F8D) is a rare,
autosomal recessive coagulation disorder in which the levels of both
coagulation factors V and VIII are diminished. The F5F8D locus was
previously mapped to a 1-cM interval on chromosome 18q21. Mutations in a candidate gene in this region, ERGIC-53, were recently found to be associated with the coagulation defect in nine Jewish families. We performed single-strand conformation and
sequence analysis of the ERGIC-53 gene in 35 F5F8D families of
different ethnic origins. We identified 13 distinct mutations
accounting for 52 of 70 mutant alleles. These were 3 splice site
mutations, 6 insertions and deletions resulting in translational
frameshifts, 3 nonsense codons, and elimination of the translation
initiation codon. These mutations are predicted to result in synthesis
of either a truncated protein product or no protein at all. This study
revealed that F5F8D shows extensive allelic heterogeneity and all
ERGIC-53 mutations resulting in F5F8D are "null." Approximately 26% of the mutations have not been identified, suggesting that lesions
in regulatory elements or severe abnormalities within the introns may
be responsible for the disease in these individuals. In two such
families, ERGIC-53 protein was detectable at normal levels in
patients' lymphocytes, raising the further possibility of defects at
other genetic loci.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Zhang, M. Spreafico, C. Zheng, A. Yang, P. Platzer, M. U. Callaghan, Z. Avci, N. Ozbek, J. Mahlangu, T. Haw, et al.
Genotype-phenotype correlation in combined deficiency of factor V and factor VIII
Blood,
June 15, 2008;
111(12):
5592 - 5600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Nyfeler, Y. Kamiya, F. Boehlen, K. Yamamoto, K. Kato, P. de Moerloose, H.-P. Hauri, and M. Neerman-Arbez
Deletion of 3 residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency
Blood,
February 1, 2008;
111(3):
1299 - 1301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Zhang, B. McGee, J. S. Yamaoka, H. Guglielmone, K. A. Downes, S. Minoldo, G. Jarchum, F. Peyvandi, N. B. de Bosch, A. Ruiz-Saez, et al.
Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2
Blood,
March 1, 2006;
107(5):
1903 - 1907.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Spatuzza, M. Renna, R. Faraonio, G. Cardinali, G. Martire, S. Bonatti, and P. Remondelli
Heat Shock Induces Preferential Translation of ERGIC-53 and Affects Its Recycling Pathway
J. Biol. Chem.,
October 8, 2004;
279(41):
42535 - 42544.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Mannucci, S. Duga, and F. Peyvandi
Recessively inherited coagulation disorders
Blood,
September 1, 2004;
104(5):
1243 - 1252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Z. Miao, N. Sirachainan, L. Palmer, P. Kucab, M. A. Cunningham, R. J. Kaufman, and S. W. Pipe
Bioengineering of coagulation factor VIII for improved secretion
Blood,
May 1, 2004;
103(9):
3412 - 3419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Nufer, S. Mitrovic, and H.-P. Hauri
Profile-based Data Base Scanning for Animal L-type Lectins and Characterization of VIPL, a Novel VIP36-like Endoplasmic Reticulum Protein
J. Biol. Chem.,
April 25, 2003;
278(18):
15886 - 15896.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Nufer, S. Guldbrandsen, M. Degen, F. Kappeler, J.-P. Paccaud, K. Tani, and H.-P. Hauri
Role of cytoplasmic C-terminal amino acids of membrane proteins in ER export
J. Cell Sci.,
January 2, 2002;
115(3):
619 - 628.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neerman-Arbez, P. de Moerloose, C. Bridel, A. Honsberger, A. Schonborner, C. Rossier, K. Peerlinck, S. Claeyssens, D. Di Michele, R. d'Oiron, et al.
Mutations in the fibrinogen Aalpha gene account for the majority of cases of congenital afibrinogenemia
Blood,
July 1, 2000;
96(1):
149 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hauri, F Kappeler, H Andersson, and C Appenzeller
ERGIC-53 and traffic in the secretory pathway
J. Cell Sci.,
January 2, 2000;
113(4):
587 - 596.
[Abstract]
[PDF]
|
|
|
|
|
|
|
K. Kaushansky
Blood: New designs for a new millennium
Blood,
January 1, 2000;
95(1):
1 - 6.
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Hedner, D. Ginsburg, J. M. Lusher, and K. A. High
Congenital Hemorrhagic Disorders: New Insights into the Pathophysiology and Treatment of Hemophilia
Hematology,
January 1, 2000;
2000(1):
241 - 265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Moussalli, S. W. Pipe, H.-P. Hauri, W. C. Nichols, D. Ginsburg, and R. J. Kaufman
Mannose-dependent Endoplasmic Reticulum (ER)-Golgi Intermediate Compartment-53-mediated ER to Golgi Trafficking of Coagulation Factors V and VIII
J. Biol. Chem.,
November 12, 1999;
274(46):
32539 - 32542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Nichols, V. H. Terry, M. A. Wheatley, A. Yang, A. Zivelin, N. Ciavarella, C. Stefanile, T. Matsushita, H. Saito, N. B. de Bosch, et al.
ERGIC-53 Gene Structure and Mutation Analysis in 19 Combined Factors V and VIII Deficiency Families
Blood,
April 1, 1999;
93(7):
2261 - 2266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
