A codon 338 nonsense mutation in the factor IX gene in unrelated hemophilia B patients: factor IX338 New York

Blood. 1989 Aug 1;74(2):737-42.


Hemophilia B is an X-linked recessive bleeding disorder resulting from a deficiency of the coagulation factor IX (FIX) protein activity, a vitamin K-dependent serine protease active in both the intrinsic and extrinsic coagulation systems. DNA analyses of the factor IX gene in two unrelated patients with severe hemophilia B, with a IX coagulant activity less than 1% and undetectable FIX antigen, detected the loss of the second TaqI site in exon h (VIII) in both individuals. Polymerase chain reaction (PCR) amplification of 576 base pairs of exon h (VIII) with cloning and dideoxy sequencing of cloned DNA from one hemophiliac revealed a single C----T transition in codon 338 that changes an arginine residue codon CGA to a nonsense codon TGA. Allele-specific oligonucleotide probe hybridization with a mutant (C----T) and a wild-type allele confirmed the same mutation in amplified genomic DNA of the second hemophilia patient. The C----T transition represents another example of mutation at a CpG dinucleotide. DNA polymorphism analysis of the FIX gene in both individuals revealed each to be on a separate FIX haplotype; therefore, predicting each to be a separate mutation event.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Codon / genetics*
  • DNA Mutational Analysis
  • Factor IX / genetics*
  • Factor IX / isolation & purification
  • Gene Amplification
  • Genes*
  • Genetic Carrier Screening
  • Hemophilia B / blood
  • Hemophilia B / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Nucleic Acid Hybridization
  • Oligonucleotide Probes
  • Pedigree
  • RNA, Messenger / genetics*
  • Restriction Mapping


  • Codon
  • Oligonucleotide Probes
  • RNA, Messenger
  • Factor IX