{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:57:51Z","timestamp":1761541071056},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,11,28]],"date-time":"2011-11-28T00:00:00Z","timestamp":1322438400000},"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":[[2012,5]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> In Haemophilia A (HA), the deficiency in coagulation factor VIII is caused by mutations in the <jats:italic>F8<\/jats:italic> gene. In the past, HA carrier detection in Iran used to be carried out by tracking polymorphic DNA markers \u2013 a technical strategy with poor efficacy and accuracy. For some 10\u2003years, however, mutations have been identified by direct DNA sequencing at the Iranian Comprehensive Haemophilia Care Centre (ICHCC), resulting in the detection of 580 different mutations and accurate carrier detection. The aim of this study was to characterize and report the unreported mutations not recorded in the <jats:italic>F8<\/jats:italic> HAMSTeRS database and HGMD, which we have detected amongst all the mutations hitherto identified. After excluding introns 1 and 22 inversions, direct DNA sequencing was used to detect mutations among our patients. These were then confirmed in another affected relative or obligate carrier. Severe cases of HA, where no mutation could be identified, were further investigated by the MLPA method. The new, unreported mutations identified include: 51 missense, 15 nonsense, 45 frame\u2010shifts, 11 splice\u2010site, 1 duplications. We report a large spectrum of mutations identified in the course of the past 10\u2003years at the ICHCC, which offers this service to all patients from regions throughout Iran. Aside from the common introns 1 and 22 inversions, this work demonstrates a high degree of heterogeneity in <jats:italic>F8<\/jats:italic> mutations. The establishment of a comprehensive Iranian HA database will improve the care and genetic counselling of Iranian HA families.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2011.02708.x","type":"journal-article","created":{"date-parts":[[2011,11,28]],"date-time":"2011-11-28T07:56:57Z","timestamp":1322467017000},"source":"Crossref","is-referenced-by-count":3,"title":["Identification of 123 previously unreported mutations in the <i>F8<\/i> gene of Iranian patients with Haemophilia A"],"prefix":"10.1111","volume":"18","author":[{"given":"S.","family":"RAVANBOD","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"RASSOULZADEGAN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"RASTEGAR\u2010LARI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"JAZEBI","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"ENAYAT","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"ALA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,11,28]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"288","article-title":"Characterization of the human factor VIII gene. 1984","volume":"24","author":"Gitschier J","year":"1992","journal-title":"Biotechnology"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.11.3983"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.1.168"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1193-236"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20596"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2004.00920.x"},{"issue":"2","key":"e_1_2_6_8_2","first-page":"317","article-title":"Detection of 101 novel mutations in the factor 8 gene of Iraninan haemophilia A patients","volume":"7","author":"Ravanbod S","year":"2009","journal-title":"J Thromb Haem"},{"key":"e_1_2_6_9_2","first-page":"612","article-title":"Proceedings: a more uniform measurement of factor VIII inhibitors","volume":"34","author":"Kasper CK","year":"1975","journal-title":"Thromb Diath Haemorrh"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1653759"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.4.6.368"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(89)90430-2"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V92.4.1458"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.02926.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05737.x"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615052"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04268.x"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01261.x"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.12427"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.1999.00352.x"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02476.x"}],"container-title":["Haemophilia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2516.2011.02708.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2516.2011.02708.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T17:30:02Z","timestamp":1698687002000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2516.2011.02708.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,28]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1111\/j.1365-2516.2011.02708.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2516.2011.02708.x","archive":["Portico"],"relation":{},"ISSN":["1351-8216","1365-2516"],"issn-type":[{"value":"1351-8216","type":"print"},{"value":"1365-2516","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11,28]]}}}