THE HIGH-FREQUENCY OF THE -6G-]A FACTOR-IX PROMOTER MUTATION IS THE RESULT BOTH OF A FOUNDER EFFECT AND RECURRENT MUTATION AT A CPG DINUCLEOTIDE

We report a new Liverpool family with a mild haemophilia B Leyden phen otype caused by a -6G --> A mutation in a CpG dinucleotide in the prom oter of the clotting factor IX gene. This mutation had previously been identified in three other U.K. pedigrees and six others worldwide, To investigate whether these mutations were of independent origin, the h aplotype was determined for eight polymorphic loci, within or immediat ely adjacent to the factor TX gene, for nine of the 10 existing patien ts. Six probands had identical haplotypes, including all four U.K. pro bands, suggesting that they arose from a common founder. The other thr ee probands differed in haplotype from the common haplotype, and from each other, suggesting that they were independent mutations at this Cp G dinucleotide.