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The molecular pathology of hemophilia






Qjm 63(242): 473-492

The molecular pathology of hemophilia

The great success of recombinant DNA technology in unravelling the pathology of the thalassaemias at a molecular level has encouraged the application of these methods to other single gene disorders of man in the hope of gaining a deeper insight into the biochemical defects underlying them. An example of this approach is provided by the sex-linked recessive disorders of blood clotting: haemophilia and Christmas disease. These clinically indistinguishable, life-long disorders result from the deficiency or abnormality of the clotting proteins factor VIII and factor IX, respectively, which both participate in the activation of factor X in the intrinsic pathway of blood coagulation. This paper looks at the information concerning the molecular biology and pathology of the haemophilias which has recently been forthcoming. The genes for factor VIII and factor IX have both been successfully cloned within the past five years, with that of factor VIII, achieved in 1984, being a particular tour de force. It encompasses 0.1 per cent of the human X chromosome and is the largest gene yet characterised. Gene cloning is the starting point from which gene probes can be designed to elucidate the molecular pathology of the haemophilias. The implications of these discoveries for the practice of clinical medicine are reviewed, with special emphasis on prenatal diagnosis and carrier detection by means of restriction fragment length polymorphisms, and replacement therapy with recombinant factor VIII.


Accession: 006719983



Related references

Lillicrap, D., 1991: The molecular pathology of hemophilia A. Transfusion Medicine Reviews 5(3): 196-206

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Antonarakis S.E.; Kazazian H.H.Jr, 1990: The molecular basis of hemophilia a factor viii deficiency in man progress report from the johns hopkins university hemophilia project baltimore maryland usa. Kasper, C K (Ed ) Progress in Clinical And Biological Research, Vol 324 Recent Advances in Hemophilia Care; Symposium, Los Angeles, California, Usa, April 13-15, 1989 Xv+341p Alan R Liss, Inc : New York, New York, Usa Illus 1-12