Novel Missense Mutation in Exon 4 of the Factor VIII : C Gene Resulting in Moderately Severe Hemophilia

H EMOPI-IILIA A, the most common congenital bleeding disorder, affects I in 10,000 to 20,000 males. The molecular lesions are heterogeneous and only I 0% of specific defects had been characterized so far. These included ddetions and point mutations.’ 8 Most of the point mutations detected involved the recognition site (TCGA) for the restriction enzyme Taq I and of these, most are associated with methylation-induced C T transitions at CpG dinucleotides in either the coding or complementary strand of DNA.’ ’8 The two exceptions were respectively G to C transversion in exon 226 and A to G substitution in exon 7#{149}7 We report a mutation of the EcoRI site (GAATTC) in exon 4 owing to C T transition at codon I 89 (TCA) of the factor VIII:C (FVIII:C) gene, confirmed by direct sequencing of polymerase chain reaction (PCR)-amplified genomic DNA.