Molecular Defect in Factor

A genomic DNA library and the enzymatic DNA amplification technique were used to isolate human factor IX coding sequences of a hemophilia Bm variant. factor lX . A point mutation that resulted in the substitution of a glutamine (CAG) for an arginine (CGG) at amino acid 180 was found in exon VI of the factor IX gene (G -p A at nucleotide 20519). This mutation alters the carboxy terminal cleavage site for the activation peptide at Argla VaIldl. The arginine residue at the activation peptide cleavage site is conserved in mouse, canine. bovine, and human factor IX, suggesting that the arginine at amino acid 1 80 is important for normal