Recovery from hemophilia B Leyden: an androgen-responsive element in the factor IX promoter.
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.
Crossley
M
M
Chemical Pathology Unit, Sir William Dunn School of Pathology, University of Oxford, United Kingdom.
Ludwig
M
M
Stowell
K M
KM
De Vos
P
P
Olek
K
K
Brownlee
G G
GG
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D005164:Factor IX / Q000502:physiology*; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D011944:Receptors, Androgen / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
C071258:LF-A1 protein, human; D011944:Receptors, Androgen; D014157:Transcription Factors; C064567:factor IX Leyden; D005164:Factor IX