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Scientific article
English

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

Published inBlood, vol. 97, no. 6, p. 1879-1881
Publication date2001
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/ genetics
  • Animals
  • Base Sequence
  • COS Cells
  • Exons/genetics
  • Fibrinogen/genetics
  • Humans
  • Molecular Sequence Data
  • Point Mutation
  • RNA Splice Sites/ genetics
  • Transfection
Citation (ISO format)
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. doi: 10.1182/blood.v97.6.1879
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ISSN of the journal0006-4971
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