A novel splicing acceptor mutation of the factor VIII gene producing skipping of exon 25
作者： J. P. Gau , H. C. Hsu , W. K. Chau , C. H. Ho
DOI: 10.1007/S00277-002-0592-Y
关键词:
摘要: A gross deletion in the factor VIII (FVIII) mRNA was determined by reverse transcriptase polymerase chain reaction (RT-PCR) for a patient with moderately severe hemophilia A. Sequencing of RT-PCR product depicted 177-bp ranging from nucleotide (nt) 6724 to nt 6900 FVIII cDNA, exactly corresponding whole exon 25. Further study genomic DNA revealed presence single base pair substitution (G >A) at position -1 intron 24. The absolute consensus AG doublet 24 splicing acceptor changed AA. In novel splice site mutation, erroneously spliced 26, skipping antigen level normal despite markedly reduced functional activity. Since 25 corresponds part C2 domain, we speculate that this aberrant domain reduces binding affinity protein phospholipid membrane, thus severely impairing function.
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