A SINGLE-BASE PAIR DELETION IN THE PROMOTER REGION OF THE FACTOR-IX GENE IS ASSOCIATED WITH HEMOPHILIA-B

Patients with the haemophilia B Leyden phenotype show a distinct patte rn of factor IX expression characterized by a post-pubertal increase i n FIX levels and the remission of clinical symptoms in adult life, Thi s phenotype has previously been linked to single base mutations within transcription factor binding sites in a region of similar to 40 bp ar ound the major start point of transcription of the FIX gene. Here we r eport 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 de letion from a triplet of thymine residues at +6 to +8. We show that th e extent to which this mutation disrupts the binding of C/EBP to its b inding site is less marked than the disruption caused by the +13 A --> G mutation of FIX Norwich (I). This correlates with age-matched pheno typic data we have available for the patient reported here and that of FIX Norwich.