Mutations of the factor VIII gene in thai hemophilia A patients

Hum Mutat. 2000 Jan;15(1):117-8. doi: 10.1002/(SICI)1098-1004(200001)15:1<117::AID-HUMU27>3.0.CO;2-E.


Hemophilia A is a common X-linked bleeding disorder caused by mutations in the coagulation factor VIII gene. The entire coding and essential sequences of the factor VIII gene were generated by a combination of genomic DNA amplification and long reverse transcription-polymerase chain reaction (long RT-PCR) using factor VIII transcripts prepared from lymphocytes. Mutations were then screened by non-radioactive single strand conformation polymorphism (SSCP) analysis and characterized by DNA sequencing. We have identified six potentially pathogenic mutations in the factor VIII gene in Thai hemophilia A patients, including two nonsense mutations (R-5X and R1966X), three missense mutations (D542Y, G1850V, and G2325C), and a 4-bp insertion (ACTA) at codon 2245. Three of these mutations (D542Y, G2325C, and 4-bp insertion) have never been previously reported, and the ins2245 is the first example of such insertion probably causing factor VIII elongation. R1966X, D542Y, G1850V, and 4-bp insertion were associated with a severe hemophiliac phenotype whereas R-5X and G2325C were observed in moderately affected patients. Mutations in the factor VIII gene in Thai hemophilia A patients are likely to be heterogeneous. This study represents the first attempt to further the understanding of the molecular basis of hemophilia A in Thai.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Ceruloplasmin / genetics
  • Factor V / genetics
  • Factor VIII / genetics*
  • Female
  • Hemophilia A / genetics*
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Swine
  • Thailand


  • Factor V
  • Factor VIII
  • Ceruloplasmin