Profiling of factor VIII mutations in Korean haemophilia A

Summary.  Haemophilia A (HA) is an X chromosome-linked inherited bleeding disorder caused by heterogeneous mutations of coagulation factor VIII (FVIII). Although more than 900 mutations of FVIII gene are reported in the HAMSTeRS database, the mutation data regarding the FVIII gene in the Korean population is currently insufficient. The aim of this study was to profile the mutations of FVIII in Korean HA, 38 unrelated Korean HA male patients were examined. Peripheral blood samples were obtained from the patients. Long distance-PCR was performed for the identification of inversions in intron 22 and intron 1. Then gross exon deletion was examined to the inversion-negative patients by multiplex-PCR. Finally, direct sequencing was performed on exons 1–26, 5'- and 3'-UTR. We identified 33 mutations from the 38 patients. These included 15 inversions in intron 22 (39.5%), one inversion in intron 1 (2.6%), one gross exon deletion (2.6%), five deletions (13.2%), two insertions (5.3%), six missense (15.8%) and three nonsense mutations (7.9%). Mutation types for five patients (13.2%) were not identified in this study. We determined that the most common defect in FVIII in this study was an inversion mutation in intron 22; this is consistent with the findings of other studies. For the first time in Korean HA, a patient with intron 1 inversion was found. In addition, we report eight novel mutation types which never been reported in HAMSTeRS database. The mutation data in this study should prove useful as a reference for the diagnosis of HA and the detection of carriers in the Korean population.