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.