Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A

Nat Genet. 1993 Nov;5(3):236-41. doi: 10.1038/ng1193-236.


Mutations in the factor VIII gene have been discovered for barely more than half of the examined cases of severe haemophilia A. To account for the unidentified mutations, we propose a model based on the possibility of recombination between homologous sequences located in intron 22 and upstream of the factor VIII gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene. We present evidence to support this model and describe a Southern blot assay that detects the inversion. These findings should be valuable for genetic prediction of haemophilia A in approximately 45% of families with severe disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Blotting, Southern
  • Cell Line, Transformed
  • Chromosome Inversion*
  • DNA Primers
  • Exons
  • Factor VIII / genetics*
  • Hemophilia A / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Recombination, Genetic


  • DNA Primers
  • Factor VIII