Molecular characterization of female hemophilia A by multiplex ligation-dependent probe amplification analysis and X-chromosome inactivation study

Blood Coagul Fibrinolysis. 2011 Apr;22(3):211-4. doi: 10.1097/MBC.0b013e328343f873.


Hemophilia A is an X-linked recessive bleeding disorder caused by mutations in the F8 gene. Hemophilia A typically occurs in male individuals, but female patients with hemophilia A have rarely been reported. Here we describe molecular characteristics of three unrelated female patients with severe hemophilia A of Korean descent. Patient 1 was a 5-year-old girl and was found to be compound heterozygous for intron 22 inversion inherited from her father with hemophilia A and a large deletion mutation from her mother. The large deletion detected by multiplex ligation-dependent probe amplification involved the whole F8 gene. Patient 2 was a 30-year-old woman and was heterozygous for small duplication mutation in exon 14 (c.3275dupA; p.Asn1092LysfsX26). Patient 3 was a 16-year-old girl and was heterozygous for intron 22 inversion. All three patients showed nonrandom X-chromosome inactivation status. The results underscore the need for a meticulous search for another mutation in the maternally derived X-chromosome such as large-dosage mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Asian People / genetics*
  • Child, Preschool
  • Chromosome Inversion
  • Factor VIII / genetics*
  • Female
  • Hemophilia A / genetics*
  • Heterozygote
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Phenotype
  • Sequence Deletion
  • X Chromosome Inactivation*


  • Factor VIII