Haemophilia B Leyden arising de novo by point mutation in the putative factor IX promoter region

Haemophilia B Leyden is characterized by severe factor IX deficiency during childhood with partial resolution at puberty or following the administration of anabolic steroids. The disorder has recently been associated with point mutations in the putative factor IX promoter region, which contains an imperfect direct repeat spanning a possible start site of transcription. We have identified a T to C transition at position +8 in the promoter region of a patient with the haemophilia B Leyden phenotype. A mutation at this site has not been previously reported and occurs within the repeat consensus sequence in the transcribed but untranslated portion of the gene. There is no family history of haemophilia and sequence analysis of his mother and other family members indicates that the mutation has arisen de novo in this patient. This observation provides further support for a causal relationship between point mutations in the presumptive promoter region of the factor IX gene and the Leyden phenotype.