1. Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins.
- Author
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Chen SH, Thompson AR, Zhang M, and Scott CR
- Subjects
- Adult, Aged, Amino Acid Sequence, Base Sequence, Chromosome Mapping, DNA analysis, Factor IX blood, Factor IX immunology, Hemophilia B immunology, Humans, Immunoelectrophoresis, Male, Molecular Sequence Data, Epitopes analysis, Factor IX genetics, Hemophilia B genetics, Mutation
- Abstract
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).
- Published
- 1989
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