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Title

Identification and functional characterization of a novel nonsense mutation in FGA accounting for congenital afibrinogenemia in six Egyptian patients

Authors
Abdel Wahab, Magy
Fish, R. J.
Published in Blood Coagulation and Fibrinolysis. 2010, vol. 21, no. 2, p. 164-167
Abstract Congenital afibrinogenemia is a rare coagulation disorder attributed to over forty mutations found either in homozygosity or in compound heterozygosity, the majority localized in FGA encoding the fibrinogen Aalpha-chain. Despite the number of genetic analyses performed the study of additional patients still allows the identification of novel mutations and a better understanding of fibrinogen structure and function. Here we report the identification and functional analysis of a novel nonsense mutation in FGA exon 5: c.718C>T (CAG>TAG) p.Q240X (Q221X in the mature chain lacking the signal peptide), accounting for fibrinogen deficiency in six Egyptian patients. Expression of the mutant Aalpha-chain cDNA in combination with wild-type Bbeta-chain and gamma-chain cDNAs demonstrated that although the mutant chain could be detected in the cell media of transfected COS-7 cells it was less secreted in comparison to the wild-type Aalpha-chain. Our patients were all homozygous for p.Q240X(Q221X) yet their clinical spectrum varied considerably in their onset of presentation or severity, with bleeding ranging from moderate mucous membrane bleeds in adolescence to life threatening intracranial hemorrhage in infancy.
Keywords AdolescentAdultAfibrinogenemia/ geneticsAnimalsCOS CellsCercopithecus aethiopsChildChild, PreschoolCodon, NonsenseDNA, Complementary/geneticsEgyptFemaleFibrinogen/ geneticsGene ExpressionHumansMaleTransfectionYoung Adult
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PMID: 20051841
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ABDEL WAHAB, Magy et al. Identification and functional characterization of a novel nonsense mutation in FGA accounting for congenital afibrinogenemia in six Egyptian patients. In: Blood Coagulation and Fibrinolysis, 2010, vol. 21, n° 2, p. 164-167. https://archive-ouverte.unige.ch/unige:8595

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Deposited on : 2010-07-12

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