LABORATORY METHODS FOR THE GENETIC DIAGNOSIS OF BLEEDING DISORDERS

Accurate carrier detection and pre-natal diagnosis in haemophilia A an d B and in von Willebrand's disease (VWD) can be achieved by genetic a nalysis. The spectrum of mutations responsible for these three disorde rs is described. Methods for linkage analysis using intragenic diallel ic and multiallelic factor VIII and IX gene polymorphisms are mentione d, and situations where their use in carrier detection is inappropriat e or fails are discussed, Linkage analysis for examination of von Will ebrand 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 discri minant test in patients with possible mild haemophilia A or VWD are de scribed. Point mutation screening methods AMD, CSGE, DGGE, SSCP and UH G analysis are also detailed. The variety of possible analyses availab le to genetically diagnose haemophilia A, B and VWD is explored.