Recombinant DNA Methods in Hemophilia A: Carrier Detection and Prenatal Diagnosis*

Abstract

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.

Using Factor VII in Hemophilia Gene Therapy

“…Ball and colleagues were used oral cells, urine and hair follicles samples to identify prenatal and carrier hemophilia A (Ball et al, 1990). Various polymorphism and mutations have been detected in FVIII gene of hemophilia A patients (Wacey et al, 1996' Antonarakis et al, 1995Naylor et al, 1991;Baranov et al, 1990;Gécz et al, 1990;Jedlicka et al, 1990;Sadler et al, 1990;Surin et al, 1990;Wehnert et al, 1990a;Wehnert et al, 1990b). Establishment the PCR technique in diagnostic laboratories was a large change in DNA analysis of FVIII gene for detecting carriers and individuals with hemophilia A (Song et al, 1993;Feng, 1991;Wadelius et al, 1991;Wu, 1991).…”