Goodeve A C
Division of Molecular and Gentic Medicine, Royal Hallamshire Hospital, Sheffield, UK.
Clin Lab Haematol. 1998 Feb;20(1):3-19. doi: 10.1046/j.1365-2257.1998.00115.x.
Accurate carrier detection and pre-natal diagnosis in haemophilia A and B and in von Willebrand's disease (VWD) can be achieved by genetic analysis. The spectrum of mutations responsible for these three disorders is described. Methods for linkage analysis using intragenic diallelic and multiallelic factor VIII and IX gene polymorphisms are mentioned, and situations where their use in carrier detection is inappropriate or fails are discussed. Linkage analysis for examination of von Willebrand factor gene inheritance in families with VWD is also described. Screening for the factor VIII gene inversion in patients with severe haemophilia A and the use of the factor VIII binding assay as a discriminant test in patients with possible mild haemophilia A or VWD are described. Point mutation screening methods AMD, CSGE, DGGE, SSCP and UHG analysis are also detailed. The variety of possible analyses available to genetically diagnose haemophilia A, B and VWD is explored.
通过基因分析可实现对甲型和乙型血友病以及血管性血友病（VWD）进行准确的携带者检测和产前诊断。文中描述了导致这三种疾病的突变谱。提及了利用基因内双等位基因和多等位基因凝血因子VIII和IX基因多态性进行连锁分析的方法，并讨论了在携带者检测中使用这些方法不恰当或失败的情况。还描述了对血管性血友病家族中血管性血友病因子基因遗传进行检测的连锁分析。介绍了对重度甲型血友病患者进行凝血因子VIII基因倒位筛查，以及将凝血因子VIII结合试验用作可能患有轻度甲型血友病或血管性血友病患者的鉴别检测方法。还详细介绍了点突变筛查方法，如扩增阻滞突变系统（AMD）、恒定变性凝胶电泳（CSGE）、变性梯度凝胶电泳（DGGE）、单链构象多态性（SSCP）和超高密度基因分型（UHG）分析。探讨了可用于对甲型、乙型血友病和血管性血友病进行基因诊断的各种可能分析方法。
