Independent occurrence of the novel Arg2163 to His mutation in the factor VIII gene in three unrelated families with haemophila A with different phenotypes. Mutations in brief no. 126. Online.

Using chemical mismatch analysis or denaturing gradient gel electrophoresis followed by nucleotide sequencing, we have identified the same G6545A mutation leading to an Arg2163 His subsitution in the factor VIII gene of three haemophiliacs from unrelated families. One of the affected individuals has severe haemophilia, while the other two are moderately severe. While we cannot exclude the possibility that these differences in phenotype arise from differences in VIII:C assay methods, other studies have also identified different clinical phenotypes in individuals with the same mutations, and suggested that they may arise from extragenic factors that affect or modify gene expression or protein function. The G6545A mutation occurs at a CG dinucleotide which is a known mutation hotspot, and which may explain the independent occurrence in unrelated families.