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Title

Mutations in the fibrinogen gene cluster accounting for congenital afibrinogenemia: an update and report of 10 novel mutations
Authors
Neerman Arbez, Marguerite
De Moerloose, Philippe
Published in Human Mutation. 2007, vol. 28, no. 6, p. 540-553
Abstract Fibrinogen is synthesized in hepatocytes in the form of a hexamer composed of two sets of three polypeptides (Aalpha, Bbeta, and gamma). Each polypeptide is encoded by a distinct gene, FGA, FGB, and FGG, all three clustered in a region of 50 kb on 4q31. Congenital afibrinogenemia is characterized by the complete absence of fibrinogen, the precursor of the major protein constituent of the blood clot, fibrin. Although the disease was first described in 1920, the genetic defect responsible for this disorder long remained unknown. We identified the gene and the first causative mutations for this disease in a nonconsanguineous Swiss family in 1999. Since this first report, 61 additional mutations, the majority in FGA, have been identified in patients with afibrinogenemia (in homozygosity or in compound heterozygosity) or in heterozygosity in hypofibrinogenemia, since many of these patients are in fact asymptomatic carriers of afibrinogenemia mutations. Mutations in the fibrinogen genes may lead to deficiency of fibrinogen by several mechanisms: these can act at the DNA level, at the RNA level by affecting mRNA splicing or stability, or at the protein level by affecting protein synthesis, assembly, or secretion. The expression of selected mutations has shown that mechanisms acting at all three levels play a role in the molecular basis of this disease. We report here the identification of 10 novel mutations, of which eight are localized in FGA, thus increasing the total number of causative mutations identified to 72 and confirming the relative importance of FGA in the molecular basis of fibrinogen deficiency.
Keywords Afibrinogenemia/ genetics — Alternative Splicing — Animals — COS Cells — Cercopithecus aethiops — Exons — Fibrinogen/biosynthesis/ genetics — Gene Expression Regulation/genetics — Humans — Multigene Family — Mutation — Polymorphism, Genetic — Sequence Deletion — Transfection
Identifiers
PMID: 17295221
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Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://www3.interscience.wiley.com/journal/114117097/abstract
Structures
Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Citation
(ISO format) 		NEERMAN ARBEZ, Marguerite, DE MOERLOOSE, Philippe. Mutations in the fibrinogen gene cluster accounting for congenital afibrinogenemia: an update and report of 10 novel mutations. In: Human Mutation, 2007, vol. 28, n° 6, p. 540-553. https://archive-ouverte.unige.ch/unige:8929

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Deposited on : 2010-07-12

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