Department of Laboratory Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo, Japan.
Int J Hematol. 2013 Jun;97(6):758-64. doi: 10.1007/s12185-013-1341-9. Epub 2013 Apr 27.
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.
血友病 A 是最常见的遗传性出血性疾病。为了更好地了解日本轻至中度血友病 A 患者的基因型和表型特征，我们研究了 29 名 FVIII:C 活性超过 1%的无亲缘关系患者。在 21 名患者中，有 9 名患者在一期凝固和显色测定法中测量的 FVIII:C 水平存在差异。我们在 29 名患者中的 28 名中鉴定了 F8 中的突变。在我们的患者中，两个氨基酸 Y492 和 R550 的突变比国际血友病 A 突变数据库中的突变频率高得多。我们证明，所有 5 名 Y492C 突变患者都具有独特的、相同的 F8 单倍型，表明该突变可能起源于一个共同的祖先。由于非重度、中度至轻度血友病患者的寿命更长，导致非重度表型的突变往往在人群中持续存在。我们认为 Y492C 突变是日本轻度血友病 A 患者的一个特征。本研究中 FVIII:C 测量差异的基础上 R550 突变的高频出现表明，日本轻度血友病患者可能需要仔细的特征描述。
