+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

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

Green P.M.; Bentley D.R.; Mibashan R.S.; Nilsson I.M.; Giannelii F., 1989: Molecular pathology of hemophilia b. Direct sequencing of amplified genomic DNA has been used to investigate the molecular basis of haemophilia B and thus identify specific amino acids that are essential for maintenance of structure or function of factor IX. Substitution of Cys 336,...

Olek, K., 1992: Molecular pathology of hemophilia A. Annals of Hematology 65(SUPPL ): A101

Gurgey, Aytemiz, 1993: Molecular pathology in hemophilia A and B, and von Willebrand disease. Cocuk Sagligi ve Hastaliklari Dergisi 36(4): 399-413

David, D.; Rosa, H.A.; Pemberton, S.; Diniz, M.J.; Campos, M.; Lavinha, J., 1993: Single-strand conformation polymorphism (SSCP) analysis of the molecular pathology of hemophilia B. In the present study, we report the application of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis to the screening of seven functionally important factor IX gene (FIX) regions (total length 2.66 kb) in 9 unre...

Caglayan, S.Hande, 1995: Molecular biology of hemophilia A and hemophilia B: Present state of DNA diagnosis in Turkey. This article begins with a short compilation of the current knowledge on the structure of factor VIII and factor IX genes and their products, an on the large number of different mutations in these genes that have been identified as causes of hemop...

Antonarakis, S.E.; Kazazian, H.H., 1990: The molecular basis of hemophilia A (factor VIII deficiency) in man; progress report from the Johns Hopkins University Hemophilia Project. Progress in Clinical and Biological Research 324: 1-11

Kojima, T., 1987: Molecular analysis and genetic diagnosis of hemophilia. b. Hemophilia B. Nihon Rinsho. Japanese Journal of Clinical Medicine 45(12): 2941-2946

Suzuki, N., 1987: Molecular analysis and genetic diagnosis of hemophilia. a. Hemophilia A. Nihon Rinsho. Japanese Journal of Clinical Medicine 45(12): 2934-2940

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