人凝血因子IX突变型研究现状

血友病B是一种性连锁隐性遗传病，其发病机制是位于X染色体上的人凝血因子IX（hFIX）基因发生了突变，导致血浆中hFIX含量或活性大幅下降，从而使得内源性凝血途径受到阻碍，无法进行正常的凝血。本文综述了hFIX基因及其编码蛋白质的结构和功能，并分类详细论述了血友病B中发现的几种主要突变类型。其中包括奠基者效应造成的突变、调控区的突变、编码区的突变、内含子剪切位点的突变及另外两种较为特殊的突变，同时介绍了这些突变所造成的生物学效应。最后还简要介绍了一种能提高hFIX蛋白凝血活性的突变类型（第338位Arg→Ala），并对其应用作了展望。

The Current Feature of the Study on Human Coagulation Factor IX Mutant

Hemophilia B is an X-linked bleeding disease, caused by the mutations of human coagulation factor IX (hFIX) gene located in chromosome X. It results in a dramatic decline of hFIX quantity or clotting activity in plasma, and the intrinsic clotting pathway is affected seriously. In this article, the structure and function of hFIX gene as well as the protein encoded by this gene were reviewed. Various types of hFIX mutants found in hemophilia B were also described, including the mutations caused by founder effects, mutations in regulatory region, coding region, splicing sites of introns and two other special mutations. Meanwhile, the biological effects of the mutations described above were discussed. Finally, a mutation type (Arg-->Ala at point 338) that can increase the clotting activity of hFIX as well as the potential application was briefly introduced.