|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 149-152
Mutations in the fibrinogen A gene account for the majority of
cases of congenital afibrinogenemia
Marguerite Neerman-Arbez,
Philippe de Moerloose,
Claire Bridel,
Ariane Honsberger,
Anni Schönbörner,
Colette Rossier,
Kathelijne Peerlinck,
Ségolène Claeyssens,
Donna Di Michele,
Roseline d'Oiron,
Marie Dreyfus,
Monique Laubriat-Bianchin,
Jacelyne Dieval,
Stylianos E. Antonarakis, and
Michael A. Morris
From the Division of Medical Genetics, University Medical
School and University Hospital, and the Division of Angiology and
Hemostasis, University Hospital, Geneva, Switzerland; the
Center for Molecular and Vascular Biology, Leuven, Belgium; the
Hemophilia Center, Hôpital Purpan, Toulouse, France; the
Department of Pediatrics, Weill Medical College of Cornell Hospital,
New York, New York; the Hemophilia Center and the
Hematology Laboratory, Hôpital Bicêtre, AP-HP
LeKremlin-Bicêtre; the Centre de Transfusion, Annecy; and the
Hematology Laboratory, CHR Amiens, France.
Congenital afibrinogenemia is a rare, autosomal, recessive disorder
characterized by the complete absence of detectable fibrinogen. We
previously identified the first causative mutations in a
nonconsanguineous Swiss family; the 4 affected persons have homozygous
deletions of approximately 11 kb of the fibrinogen alpha (FGA)
gene. Haplotype data implied that these deletions occurred on distinct
ancestral chromosomes, suggesting that this region may be susceptible
to deletion by a common mechanism. We subsequently showed that all the
deletions were identical to the base pair and probably resulted from a
nonhomologous recombination mediated by 7-bp direct repeats. In this
study, we have collected data on 13 additional unrelated patients to
identify the causative mutations and to determine the prevalence of the
11-kb deletion. A common recurrent mutation, at the donor splice site
of FGA intron 4 (IVS4 + 1 G > T), accounted for 14 of the
26 (54%) alleles. One patient was heterozygous for the previously
identified deletion. Three more frameshift mutations, 2 nonsense
mutations, and a second splice site mutation were also identified.
Consequently, 86% of afibrinogenemia alleles analyzed to date have
truncating mutations of FGA, though mutations in all 3 fibrinogen genes, FGG, FGA, and FGB, might be predicted to cause congenital afibrinogenemia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
R. Park, H.-J. Doh, S.-S. A. An, J.-R. Choi, K.-H. Chung, and K.-S. Song
A novel fibrinogen variant (fibrinogen Seoul II; A{alpha}Gln328Pro) characterized by impaired fibrin {alpha}-chain cross-linking
Blood,
September 15, 2006;
108(6):
1919 - 1924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Vu, C. Di Sanza, D. Caille, P. de Moerloose, H. Scheib, P. Meda, and M. Neerman-Arbez
Quality control of fibrinogen secretion in the molecular pathogenesis of congenital afibrinogenemia
Hum. Mol. Genet.,
November 1, 2005;
14(21):
3271 - 3280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D Vu, P de Moerloose, A Batorova, J Lazur, L Palumbo, and M Neerman-Arbez
Hypofibrinogenaemia caused by a novel FGG missense mutation (W253C) in the {gamma} chain globular domain impairing fibrinogen secretion
J. Med. Genet.,
September 1, 2005;
42(9):
e57 - e57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neerman-Arbez, M. Germanos-Haddad, K. Tzanidakis, D. Vu, S. Deutsch, A. David, M. A. Morris, and P. de Moerloose
Expression and analysis of a split premature termination codon in FGG responsible for congenital afibrinogenemia: escape from RNA surveillance mechanisms in transfected cells
Blood,
December 1, 2004;
104(12):
3618 - 3623.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Lefebvre, P. T. Velasco, A. Dear, K. C. Lounes, S. T. Lord, S. O. Brennan, D. Green, and L. Lorand
Severe hypodysfibrinogenemia in compound heterozygotes of the fibrinogen A{alpha}IVS4 + 1G>T mutation and an A{alpha}Gln328 truncation (fibrinogen Keokuk)
Blood,
April 1, 2004;
103(7):
2571 - 2576.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Vu, P. H. B. Bolton-Maggs, J. R. Parr, M. A. Morris, P. de Moerloose, and M. Neerman-Arbez
Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion
Blood,
December 15, 2003;
102(13):
4413 - 4415.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Neerman-Arbez, D. Vu, B. Abu-Libdeh, I. Bouchardy, and M. A. Morris
Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense mutation in the FGB gene in a Palestinian family
Blood,
May 1, 2003;
101(9):
3492 - 3494.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Attanasio, A. David, and M. Neerman-Arbez
Outcome of donor splice site mutations accounting for congenital afibrinogenemia reflects order of intron removal in the fibrinogen alpha gene (FGA)
Blood,
March 1, 2003;
101(5):
1851 - 1856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Spena, S. Duga, R. Asselta, M. Malcovati, F. Peyvandi, and M. L. Tenchini
Congenital afibrinogenemia: first identification of splicing mutations in the fibrinogen Bbeta -chain gene causing activation of cryptic splice sites
Blood,
December 15, 2002;
100(13):
4478 - 4484.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Okumura, F. Terasawa, H. Tanaka, M. Hirota, H. Ota, K. Kitano, K. Kiyosawa, and S. T. Lord
Analysis of fibrinogen gamma -chain truncations shows the C-terminus, particularly gamma Ile387, is essential for assembly and secretion of this multichain protein
Blood,
May 15, 2002;
99(10):
3654 - 3660.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Iwaki, M. J. Sandoval-Cooper, M. Paiva, T. Kobayashi, V. A. Ploplis, and F. J. Castellino
Fibrinogen Stabilizes Placental-Maternal Attachment During Embryonic Development in the Mouse
Am. J. Pathol.,
March 1, 2002;
160(3):
1021 - 1034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Asselta, S. Duga, S. Spena, E. Santagostino, F. Peyvandi, G. Piseddu, R. Targhetta, M. Malcovati, P. M. Mannucci, and M. L. Tenchini
Congenital afibrinogenemia: mutations leading to premature termination codons in fibrinogen Aalpha -chain gene are not associated with the decay of the mutant mRNAs
Blood,
December 15, 2001;
98(13):
3685 - 3692.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Attanasio, P. de Moerloose, S. E. Antonarakis, M. A. Morris, and M. Neerman-Arbez
Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G{right-arrow}T
Blood,
March 15, 2001;
97(6):
1879 - 1881.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Asselta, S. Duga, T. Simonic, M. Malcovati, E. Santagostino, P. L. F. Giangrande, P. M. Mannucci, and M. L. Tenchini
Afibrinogenemia: first identification of a splicing mutation in the fibrinogen gamma chain gene leading to a major gamma chain truncation
Blood,
October 1, 2000;
96(7):
2496 - 2500.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
