{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T04:25:45Z","timestamp":1793939145757,"version":"4.8.0"},"reference-count":51,"publisher":"Wiley","issue":"s4","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> 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 <jats:italic>de novo<\/jats:italic> in early embryogenesis from somatic mutations, a finding that has implications for genetic counselling. The life\u2010cycle of the FVIII protein and its structure\u2010function relationships are continuously clarified. Most recently it has been shown that FVIII clearance from the circulation is mediated by the low\u2010density lipoprotein receptor\u2010related protein (LRP) and cell\u2010surface heparan sulphate proteoglycans (HSPGs). These findings raise hope for novel recombinant FVIII molecules with prolonged half\u2010life that may improve therapies for haemophlia A.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2004.01005.x","type":"journal-article","created":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T16:04:19Z","timestamp":1097251459000},"page":"133-139","source":"Crossref","is-referenced-by-count":79,"title":["Molecular basis of haemophilia A"],"prefix":"10.1111","volume":"10","author":[{"given":"J.","family":"Oldenburg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. M.","family":"Ananyeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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