Hemofilia A: análisis de intron 18 e intron 7 del gen del factor VIII y su rol en una estrategia de diagnóstico de portadoras en una población chilena / Hemophilia A: analysis of intron 18 and intron 7 of factor VIII gene and its role in a strategy of carrier diagnosis in a chilean population

ABSTRACT

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. A large number of different mutations in the VIII gene have been identified. Thus, the detection of female carriers, depends upon the analysis of DNA polymorphism in and near the factor VIII gene. Our aim was to develop a strategy, earlier reported, for carrier testing in families at risk of hemophilia A. In this study, we analyzed the DNA polymorphisms in 26 affected families, with use of the factor VIII intragenic polymorphisms identified by the restriction enzymes Bcll and AlwNI and by differential hybridization with sequence-specific oligonuclaotide probes recognizing Bcll and AlwNI polymorphisms. While the DNA polymorphism detected by Bcll site in intron 18 of the factor VIII gene was informative for 30 percent families studied, the AlwNI/intron 7 polymorphism provided aditional information (4 percent). The carrier status of the remaining 58 percent could be determined utilizing the other polymorphisms suggested the strategy. The 2 polymorphic sites used combined with the other polymorphisms, intragenic and extragenic, can generate levels of informativeness greater than 98 percent. We concluded that the strategy for carrier testing would be a good alternative in genetic counselling for hemophilia A., but its limitations must be carefully taken into account