A novel splicing mutation in F8 causes various aberrant transcripts in a hemophilia A patient and identifies a new transcript from healthy individuals

: Hemophilia A is an X-linked hemorrhagic disorder caused by deficiency or dysfunction of the coagulation factor VIII (FVIII), and a great variety of mutations in the factor VIII gene (F8) are identified. We aimed to identify the genetic defects of the F8 gene in a Chinese patient with moderate hemophilia A. We have identified a novel intronic variant in the hemophilia A patient by DNA sequence analysis, cDNA sequencing, and TA clone sequencing. An intronic variant, c.5816-1G>A, was identified and the cDNA sequencing confirmed the pathogenicity of the transition. TA clone sequencing showed that the splicing mutation produced two aberrant premRNA skipping exons (18 and exon 18 + 19, respectively). These aberrant mRNA forms maintain the reading frame and are predicted to code for deleted FVIII isoforms and the shorter abnormal transcript accounted for one-eighth of the total mRNA. There was a new unreported transcript with E22 spliced out in healthy individuals and our patient, whose specific functions need to be determined in further studies. Our study widens the mutation spectrum of the F8 gene. In addition, the study findings could provide the opportunity to reveal alternative splicing patterns.