title: Molecular characterization of female hemophilia A by multiplex ligation-dependent probe amplification analysis and X-chromosome inactivation study.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Song
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: In-Ae
authors.initials: IA
authors.lastname: Park
authors.forename: Ki-O
authors.initials: KO
authors.lastname: Lee
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D007446:Chromosome Inversion; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017384:Sequence Deletion; D049951:X Chromosome Inactivation
chemical_list: D005169:Factor VIII