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Molecular basis of haemophilia A
Author(s) -
Oldenburg J.,
Ananyeva N. M.,
Saenko E. L.
Publication year - 2004
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2004.01005.x
Subject(s) - haemophilia , haemophilia a , somatic cell , medicine , mutation , recombinant dna , gene , receptor , ldl receptor , lipoprotein , genetics , microbiology and biotechnology , cancer research , immunology , biology , endocrinology , cholesterol , pediatrics
Summary. Technologies in molecular biology have greatly advanced the knowledge regarding the origin of haemophilia A and the physiology of the factor VIII (FVIII) protein. A variety of different mutations in the FVIII gene have been identified and their effects on the FVIII protein described. It has been shown that the frequency of haemophilia A is due to a high mutation rate predominantly in male germ cells. A significant proportion is originating de novo in early embryogenesis from somatic mutations, a finding that has implications for genetic counselling. The life‐cycle of the FVIII protein and its structure‐function relationships are continuously clarified. Most recently it has been shown that FVIII clearance from the circulation is mediated by the low‐density lipoprotein receptor‐related protein (LRP) and cell‐surface heparan sulphate proteoglycans (HSPGs). These findings raise hope for novel recombinant FVIII molecules with prolonged half‐life that may improve therapies for haemophlia A.