Haemophilia A is an X-linked bleeding disorder caused by mutations in the coagulation factor VIII (FVIII) gene. The identification and characterization of naturally occurring disease-producing mutations allows the recognition of new mechanisms of pathogenesis in haemophilia A. Analysis of the illegitimately transcribed FVIII mRNA in a severely affected patient has revealed that the A→G transition at position −2 of the acceptor splice site of intron 4 results in the skipping of exon 5 in 90% of the processed pre-mRNA. Another minor mRNA species arising from the skipping of exons 4 and 5 has also been observed. The skipping of exon 5 predicts the removal of the corresponding 13 amino acids from the A1 domain of FVIII. A novel missense mutation, C329S, in exon 8 of FVIII gene has been identified in another patient.
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David, D., Tavares, A. & Lavinha, J. Characterization of a splicing mutation in the factor VIII gene at the RNA level. Hum Genet 95, 109–111 (1995). https://doi.org/10.1007/BF00225086
- Internal Medicine
- Metabolic Disease
- Missense Mutation
- Splice Site
- Factor VIII