Exon skipping caused by an intronic insertion of a young Alu Yb9 element leads to severe hemophilia A

Hum Genet. 2003 Sep;113(4):348-52. doi: 10.1007/s00439-003-0986-5. Epub 2003 Jul 12.


Short interspersed elements, such as Alu elements, have propagated to more than one million copies in the human genome. They affect the genome in several ways, caused by retrotransposition, recombination between elements, gene conversion, and alterations in gene expression. These events, including novel insertions into active genes, have been associated with a number of human disorders. Hemophilia A is an X-linked severe bleeding disorder and is caused by mutations in the Factor VIII gene. The spectrum of mutations includes point mutations, rearrangements, insertions, and deletions. Recently, an Alu retrotransposition event in a coding exon has been reported in a family with a severe form of hemophilia A. This was the first report of an Alu insertion in the Factor VIII gene. Here, we report a second Alu insertion event that lies in an intron of the same gene that causes exon skipping and the complete disruption of gene expression.

MeSH terms

  • Alternative Splicing*
  • Alu Elements*
  • Base Sequence
  • Child
  • Exons
  • Hemophilia A / genetics*
  • Humans
  • Introns
  • Male
  • Molecular Sequence Data
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA