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Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G→T

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Published in Blood. 2001, vol. 97, no. 6, p. 1879-1881
Abstract Our recent studies on the molecular basis of the autosomal recessive disorder congenital afibrinogenemia showed that the most common mutation is a donor splice mutation in FGA intron 4, IVS4 + 1 G→T, accounting for approximately half of disease alleles. The effect of this mutation on messenger RNA (mRNA) splicing, however, remained unproven. COS-7 cells transfected with a normal plasmid construct produced 100% mRNA molecules with correct splicing, whereas cells transfected with a mutant construct produced multiple aberrant mRNAs, due to utilization of cryptic donor splice sites situated in exon 4 and intron 4. One particular site situated 4 base pairs (bp) downstream of the normal site was used in 85% of transcripts causing afibrinogenemia by a 4-bp insertion-frameshift, leading to premature alpha-chain truncation. Our results confirm the utility of transfecting COS-7 cells to study mRNA splice-site mutations and demonstrate that the common FGA IVS4 variant is a null mutation leading to afibrinogenemia.
Keywords Afibrinogenemia/congenital/etiology/ geneticsAnimalsBase SequenceCOS CellsExons/geneticsFibrinogen/geneticsHumansMolecular Sequence DataPoint MutationRNA Splice Sites/ geneticsTransfection
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PMID: 11238133
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ATTANASIO, Catia et al. Activation of multiple cryptic donor splice sites by the common congenital afibrinogenemia mutation, FGA IVS4 + 1 G→T. In: Blood, 2001, vol. 97, n° 6, p. 1879-1881. https://archive-ouverte.unige.ch/unige:8619

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Deposited on : 2010-07-12

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