Characterization of a splicing mutation in the factor VIII gene at the RNA level.
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.
David
D
D
Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.
Tavares
A
A
Lavinha
J
J
D001483:Base Sequence; D004247:DNA; D004252:DNA Mutational Analysis; D005169:Factor VIII / Q000235:genetics*; D006467:Hemophilia A / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*
D012333:RNA, Messenger; D005169:Factor VIII; D004247:DNA