Three point mutations in the factor IX genes of five hemophilia B patients. Identification strategy using localization by altered epitopes in their hemophilic proteins.
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).
Chen
S H
SH
Department of Pediatrics, University of Washington, Seattle 98195.
Thompson
A R
AR
Zhang
M
M
Scott
C R
CR
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D000939:Epitopes / Q000032:analysis*; D005164:Factor IX / Q000097:blood / Q000235:genetics* / Q000276:immunology; D002836:Hemophilia B / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007122:Immunoelectrophoresis; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation
D000939:Epitopes; D005164:Factor IX; D004247:DNA