A single base pair deletion in the promoter region of the factor IX gene is associated with haemophilia B.
Patients with the haemophilia B Leyden phenotype show a distinct pattern of factor IX expression characterized by a post-pubertal increase in FIX levels and the remission of clinical symptoms in adult life. This phenotype has previously been linked to single base mutations within transcription factor binding sites in a region of approximately 40 bp around the major start point of transcription of the FIX gene. Here we report a novel mutation in this region within the transcription factor C/EBP binding site at +1 to +18. The mutation is a single base pair deletion from a triplet of thymine residues at +6 to +8. We show that the extent to which this mutation disrupts the binding of C/EBP to its binding site is less marked than the disruption caused by the +13 A-->G mutation of FIX Norwich (1). This correlates with age-matched phenotypic data we have available for the patient reported here and that of FIX Norwich.
Hall
A J
AJ
Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield, UK.
Chuansumrit
A
A
Peake
I R
IR
Winship
P R
PR
D001482:Base Composition / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D005164:Factor IX / Q000235:genetics*; D017353:Gene Deletion; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D005164:Factor IX