[Hemophilia A: analysis of intron 18 and intron 7 of factor VIII gene and their role in a diagnostic strategy for carrier detection in a Chilean population].

Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. A larger number of different mutations in the VIII gene have been identified. Thus, the detection of female carriers, depends upon the analysis of DNA polymorphisms 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 BclI and AlwNI, and by differential hybridization with sequence-specific oligonucleotide probes recognizing BclI and AlwNI polymorphism. While the DNA polymorphism detected by BcilI site in intron 18 of the factor VIII gene was informative for 38% families studied, the AlwNI/intron 7 polymorphism provided additional information (4%). The carrier status of the remaining 58% could be determined utilizing the other polymorphisms suggested by strategy. The two polymorphic sites used combined with the other polymorphisms, intragenic and extragenic, can generate levels of informativeness greater than 98%. 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.