title: Genotypic and phenotypic features of Japanese patients with mild to moderate hemophilia A.
abstract: Hemophilia A is the most common inherited bleeding disorder. To better understand the genotypic and phenotypic features of Japanese patients with mild to moderate hemophilia A, we studied 29 unrelated patients with more than 1 % FVIII activity (FVIII:C). Differences were observed in nine of 21 patients in measured FVIII:C levels between the one-stage clotting and chromogenic assays. We identified a mutation in F8 in 28 of the 29 patients. Mutations in two amino acids, Y492 and R550, were detected at a much higher frequency in our patients than in the international hemophilia A mutation database. We demonstrated that all five patients with the Y492C mutation have an identical F8 haplotype that is unique to them, suggesting that the mutation may have originated from a common ancestor. Because non-severe, moderate to mild, hemophilia patients have a longer lifespan, mutations that cause non-severe phenotypes tend to persist in the population. We believe that the Y492C mutation is a distinctive feature of Japanese patients with mild hemophilia A. The identification of a high frequency of R550 mutation that underlies the discrepancies in FVIII:C measurements in the present study suggests that Japanese patients with mild hemophilia may require careful characterization.
authors.affiliation: Department of Laboratory Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, Japan. hrsinb@tokyo-med.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inaba
authors.forename: Keiko
authors.initials: K
authors.lastname: Shinozawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Seita
authors.forename: Manabu
authors.initials: M
authors.lastname: Otaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hagiwara
authors.forename: Kagehiro
authors.initials: K
authors.lastname: Amano
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Fukutake
mesh_terms: D044466:Asian People / Q000235:genetics*; D001777:Blood Coagulation; D005169:Factor VIII / Q000235:genetics* / Q000378:metabolism*; D056726:Genetic Association Studies; D005838:Genotype; D006467:Hemophilia A / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
chemical_list: D005169:Factor VIII