{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T23:23:40Z","timestamp":1750202620394},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:00:00Z","timestamp":1337731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> We performed molecular analysis of the <jats:italic>factor 8<\/jats:italic> gene (<jats:italic>F8<\/jats:italic>) in 272 unrelated Spanish patients with haemophilia A (HA) and detected a mutation by routine analysis in 267 of them (98.1%). No mutation was detected in the remaining five patients despite clinical and laboratory confirmation of HA. The aim is to describe the molecular alterations in <jats:italic>F8<\/jats:italic> discovered by gene dosage methodologies in three of these patients. For methodology, <jats:italic>F8<\/jats:italic> sequencing, intragenic marker analysis, multiplex ligation\u2010dependent probe amplification and quantitative real time\u2010PCR were followed. One patient had Klinefelter syndrome (47,XXY) and a large deletion spanning exons 1\u201312 masked by the other <jats:italic>F8<\/jats:italic> allele; the second patient showed a large duplication spanning exons 2\u201310 and the third patient revealed a non\u2010contiguous double duplication of exons 14 and 23\u201325. The remaining two patients had mild HA and dosage results were normal. The application of gene dosage methods is useful to define haemophilic patients in whom mutations are not detected using other routine methods. Nevertheless, in a small percentage of patients (&lt;1%), no molecular pathology can be identified after testing several genetic methodologies.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2012.02818.x","type":"journal-article","created":{"date-parts":[[2012,5,24]],"date-time":"2012-05-24T03:49:44Z","timestamp":1337831384000},"page":"708-713","source":"Crossref","is-referenced-by-count":6,"title":["<i>F8<\/i> gene dosage defects in atypical patients with severe haemophilia A"],"prefix":"10.1111","volume":"18","author":[{"given":"A.","family":"VENCESL\u00c1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"BAENA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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