of the factor IX gene in four families with hemophilia B

Hemophilia B is an X-linked coagulopathy caused by defects in the factor IX gene. We have examined the putative promoter region, the coding sequence, and splice junctions in 320 consecutive families with hemophilia B. Mutations have been found in all but 18 of these families (94%). In the search for the undefined mutations in these 18 cases, the region adjacent to the polyadenylation site was sequenced. In four families (HB95, HB150, HB263, and HB318), an A to G transition was detected at base pair 32,528 [numbering system from (1)], 208 bp 5 ' of the polyadenylation signal. This transition creates a potential splice donor site in the 3 ' untranslated region of the factor IX gene (Figure 1). The affected individuals have clinically severe disease associated with factor IX coagulants of less than 3 %, and factor IX antigens of less than 1 % (except for HB318 for whom dat