血友病A发病分子机制的研究现状

Research Status of Molecular Pathogenesis of Hemophilia A

血友病A的发病机制是凝血因子Ⅷ(FⅧ)基因的各种突变导致FⅧ活性降低,错义突变是轻/中型血友病A发病的主要机制,内含子22的倒位是重型血友病A发病的主要机制。无义突变、剪接位点突点、片段缺失、插入突变占已知突变的其余部分。突变产生的效应包括产生功能缺陷的FⅧ或减少循环中FⅧ的数量。大部分的基因突变已经确定,仍有少量患者检测不到FⅧ基因的突变。该文就血友病A的发病机制予以综述。

Hemophilia A is caused by a wide spectrum of different mutations in the factor Ⅷ gene,leading to deficiencies in coagulation FⅧ activity. Missense mutations are the main mechanism for mild/moderate haemophilia A,while intron 22 inversion is the main mechanism for the pathogenesis of severe hemophilia. Nonsense mutation,splice site mutation,fragment deletion,insertion mutation account for the rest known mutations. The effects that mutations produce contain generating functional defected F Ⅷ or reducing the quantity of the F Ⅷ in circulation. Most of the gene mutations have been identified,while mutation of F Ⅷ gene are still not detected in a small number of patients. Here is to make a review of the pathogenesis of hemophilia A.