Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter

Science. 1992 Jul 17;257(5068):377-9. doi: 10.1126/science.1631558.

Abstract

One form of the inherited, X-linked, bleeding disorder, hemophilia B, resolves after puberty. Mutations at -20 and -26 in the clotting factor IX promoter impair transcription by disrupting the binding site for the liver-enriched transcription factor LF-A1/HNF4. The -26 but not the -20 mutation also disrupts an androgen-responsive element, which overlaps the LF-A1/HNF4 site. This explains the improvement seen in patients with the -20 mutation and the failure of the -26 patient to recover.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites / genetics
  • Binding, Competitive
  • Cloning, Molecular
  • Electrophoresis, Polyacrylamide Gel
  • Factor IX / physiology*
  • Hemophilia B / genetics*
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic / physiology*
  • Receptors, Androgen / metabolism
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transfection

Substances

  • LF-A1 protein, human
  • Receptors, Androgen
  • Transcription Factors
  • factor IX Leyden
  • Factor IX