|
|
Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-10-3116.
Submitted October 21, 2002
Accepted December 13, 2002
Prenatal diagnosis for congenital afibrinogenemia caused by a novel nonsense mutation in the FGB gene in a Palestinian family
Marguerite Neerman-Arbez*, Dung Vu, Bassam Abu-Libdeh, Isabelle Bouchardy, and Michael A Morris
Division of Medical Genetics, University Medical School and University Hospital, Geneva, Switzerland
Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland
Departement of Pediatrics and Genetics, Makassed Hospital, Jerusalem, Israel
* Corresponding author; email: Marguerite.Arbez{at}medecine.unige.ch.
Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease, these were homozygous deletions of approximately 11 kb of the fibrinogen alpha chain gene (FGA). Subsequent analyses revealed that the great majority of afibrinogenemia alleles are truncating mutations of FGA, although mutations in all three fibrinogen genes, FGG, FGA and FGB have been identified. In this study, we performed the first prenatal diagnosis for afibrinogenemia. The causative mutation in a Palestinian family was a novel nonsense mutation in the FGB gene, W467X. Expression of the W467X mutant FGB cDNA in combination with wild-type FGA and FGG cDNAs showed that fibrinogen molecules containing the mutant beta-chain are not secreted into the media. The fetus was found to be heterozygous for the W467X mutation by direct sequencing and by linkage analysis, a result which was confirmed in the new-born by intermediate fibrinogen levels.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
D. Vu, C. Di Sanza, and M. Neerman-Arbez
Manipulating the quality control pathway in transfected cells: low temperature allows rescue of secretion-defective fibrinogen mutants
Haematologica,
February 1, 2008;
93(2):
224 - 231.
[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. M. Mannucci, S. Duga, and F. Peyvandi
Recessively inherited coagulation disorders
Blood,
September 1, 2004;
104(5):
1243 - 1252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. W. Mosesson
Afibrinogenemia in a compound heterozygote: making sense out of missense
Blood,
December 15, 2003;
102(13):
4247 - 4248.
[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]
|
|
|
|
|
