A novel haemophilia B defect due to partial duplication of the factor IX gene

Br J Haematol. 1994 Mar;86(3):601-9. doi: 10.1111/j.1365-2141.1994.tb04792.x.

Abstract

A patient with mild FIX deficiency was found to have partial duplication of the 3' region of the gene, giving, in addition to the a normal gene, another piece of DNA containing exons 5', 6', 7' and 8' and the intervening sequences. Cloning and sequencing of the junction region revealed that crossover occurred at nt 31927 in the 3' untranslated region of one chromosome/chromatid and nt 10640 in intron 4 of the other. No homology or topoisomerase specific sequences were observed in the crossover region. PCR and sequencing of illegitimate FIX transcripts from the patient's lymphocytes showed at least three different species of mRNAs. Translation of two of these 'novel' mRNAs should result in truncated proteins. Possibilities for the splicing of the mature mRNA are offered to explain the translation of a normal-size FIX protein, which was the only product demonstrated on Western blot analysis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • DNA / chemistry
  • DNA Transposable Elements / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Exons / genetics
  • Factor IX / analysis
  • Factor IX / genetics*
  • Factor IX / immunology
  • Hemophilia B / blood
  • Hemophilia B / genetics*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Multigene Family*
  • Polymerase Chain Reaction
  • RNA, Messenger / chemistry

Substances

  • DNA Transposable Elements
  • RNA, Messenger
  • Factor IX
  • DNA