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Title

Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion

Authors
Bolton-Maggs, P. H.
Parr, J. R.
Published in Blood. 2003, vol. 102, no. 13, p. 4413-4415
Abstract Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease: a homozygous deletion of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Subsequent studies revealed that the great majority of afibrinogenemia mutations are localized in FGA, but mutations were also found in FGG and FGB. Apart from 3 missense mutations identified in the C-terminal portion of FGB, all fibrinogen gene mutations responsible for afibrinogenemia are null. In this study, a young boy with afibrinogenemia was found to be a compound heterozygote for 2 mutations in FGB: an N-terminal nonsense mutation W47X (exon 2) and a missense mutation (G444S, exon 8). Coexpression of the FGB G444S mutant cDNA in combination with wild-type FGA and FGG cDNAs demonstrated that fibrinogen molecules containing the mutant beta chain are able to assemble but are not secreted into the media, confirming the pathogenic nature of the identified mutation.
Keywords AdultAfibrinogenemia/ geneticsAmino Acid SequenceAmino Acid SubstitutionAnimalsCOS CellsCercopithecus aethiopsCodon, NonsenseExons/geneticsFemaleFibrinogen/chemistry/ genetics/ secretionHeterozygoteHumansInfant, NewbornMaleMolecular Sequence DataMutation, MissensePedigreeProtein FoldingProtein Structure, TertiarySequence AlignmentSequence Homology, Amino AcidTransfection
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PMID: 12893758
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VU, Dung et al. Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion. In: Blood, 2003, vol. 102, n° 13, p. 4413-4415. https://archive-ouverte.unige.ch/unige:9079

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Deposited on : 2010-07-12

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