Factor IX Chongqing: a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B

Thromb Haemost. 1990 Feb 19;63(1):24-6.


A Chinese patient with sporadic, severe hemophilia B was found to have a low level of total factor IX antigen (3.5 U/dl), but less apparent antigen in an assay using a calcium-dependent antibody fraction (1.1 U/dl). This suggested a defect in the factor IX Gla domain coded mainly by exon 2 of the factor IX gene. Exon 2 was therefore amplified and sequenced. An A to T substitution was found at nucleotide 6455 of the patient's factor IX gene. This transversion changes the codon for Glu 27 in normal factor IX to a codon for Val. Since Glu 27 becomes an essential Gla residue, the defect should result in altered calcium-binding or calcium-dependent conformation of the patient's factor IX. The introduction of a hydrophobic side chain also appears to affect the hemophilic protein's stability. In leukocyte DNA from the patient's mother, the nucleotide sequence of exon 2 was entirely normal. Thus, barring somatic mosaicism within her germ cells, the new mutation occurred in oogenesis of her ovary.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Calcium-Binding Proteins / genetics*
  • Child
  • Exons
  • Factor IX / genetics*
  • Hemophilia B / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation


  • Calcium-Binding Proteins
  • factor IX Chongqing
  • Factor IX