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

M. C. Driscoll, E. Bouhassira, L. M. Aledort

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Abstract

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 < 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.

Original languageEnglish (US)
Pages (from-to)737-742
Number of pages6
JournalBlood
Volume74
Issue number2
StatePublished - Jan 1 1989

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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