Sadler J E
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Semin Thromb Hemost. 1990 Oct;16(4):341-7. doi: 10.1055/s-2007-1002687.
Hemophilia A is a serious inherited bleeding disorder of man that is caused by deficiency of blood coagulation Factor VIII. Major clinical problems in the treatment of hemophilia A include the transmission of disease by therapeutic blood products and the development of alloantibody inhibitors to transfused Factor VIII. The genetic counseling of affected families is made more difficult by the inherent inaccuracy of carrier detection based on plasma Factor VIII levels. The cloning of genomic DNA and cDNA for human Factor VIII has been a starting point for at least a partial solution to each of these problems. Determination of the Factor VIII gene structure has elucidated the cause of hemophilia A in several patients. RFLPs within or near the Factor VIII gene have provided genetic markers that allow unambiguous assignment of carrier status and accurate prenatal diagnosis. This is generally accomplished by restriction enzyme digestion and Southern blotting of genomic DNA with Factor VIII probes. At present, a high degree of skill is required to perform and interpret these tests. The use of the so-called PCR method for the amplification of specific genomic DNA fragments promises to make these analyses faster and less technically demanding.
甲型血友病是一种严重的人类遗传性出血性疾病，由血液凝固因子VIII缺乏引起。甲型血友病治疗中的主要临床问题包括治疗性血液制品传播疾病以及对输注的因子VIII产生同种异体抗体抑制剂。基于血浆因子VIII水平的携带者检测存在固有误差，这使得对受影响家庭的遗传咨询变得更加困难。人类因子VIII基因组DNA和cDNA的克隆是至少部分解决这些问题的起点。因子VIII基因结构的确定阐明了数名患者患甲型血友病的原因。因子VIII基因内部或附近的限制性片段长度多态性（RFLPs）提供了遗传标记，可明确确定携带者状态并进行准确的产前诊断。这通常通过用因子VIII探针进行基因组DNA的限制性酶切消化和Southern印迹来完成。目前，进行和解释这些检测需要高度的技巧。使用所谓的聚合酶链反应（PCR）方法扩增特定的基因组DNA片段有望使这些分析更快且对技术要求更低。
