Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins

J Clin Invest. 1989 Jul;84(1):113-8. doi: 10.1172/JCI114130.


In five patients with hemophilia B and detectable Factor IX antigen, altered reactivity to a specific polyclonal antibody fraction or monoclonal anti-Factor IX antibodies was noted. Amplification of selected portions of their Factor IX genes by polymerase chain reaction allowed rapid identification of a single base transition in each of the five families tested. In a patient with severe hemophilia and an altered calcium binding domain, a G to A transition in exon II changed the codon for Glu-27 to Lys (Factor IXSeattle 3). Patients from two families with mild hemophilia with decreased reactivity to a MAb that binds to a site within the sequence coded for by exon IV had a G to A transition changing the codon for Gly-60 to Ser (Factor IXDurham). Two unrelated patients with moderately severe hemophilia lacked reactivity to another murine monoclonal anti-Factor IX which binds to an epitope in the amino-terminal half of the heavy chain of Factor IXa. In these patients, exon VIII contained a G to A transition changing Arg-248 to Gln (Factor IXSeattle 4).

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • DNA / analysis
  • Epitopes / analysis*
  • Factor IX / blood
  • Factor IX / genetics*
  • Factor IX / immunology
  • Hemophilia B / genetics*
  • Hemophilia B / immunology
  • Humans
  • Immunoelectrophoresis
  • Male
  • Molecular Sequence Data
  • Mutation*


  • Epitopes
  • Factor IX
  • DNA

Associated data

  • GENBANK/M11309