Mutation analysis of factor VIII in Korean patients with severe hemophilia A

Hemophilia A is an X-linked recessive disorder caused by mutations of the factor VIII gene. The mutation spectrum has been reported in various populations, but not in Koreans. Mutation analysis of the factor VIII gene was performed in 22 unrelated Korean patients with severe hemophilia A. We extracted genomic DNA from their blood, and assessed intron inversions, deletions, and point mutations by direct DNA sequencing. A multiplex ligation-dependent probe amplification gene dosage assay was also performed to identify exon deletions. Disease-causing mutations were identified in all patients, of which four cases were previously unreported. Seven intron 22 inversions, nine point mutations (6 nonsense mutations and 3 missense mutations), and four small rearrangements were identified. One multi-exon deletion and one 5′-donor splicing site mutation were also observed. Four novel mutations (one small deletion, one multiple exon deletion, one missense, and one splice site mutation) were detected, and point mutations were predominant (40.9%), followed by intron 22 inversions (31.8%). Further studies are required in order to establish a solid conclusion regarding the prevalence of various mutations in the Korean population.