{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:15:37Z","timestamp":1783149337109,"version":"3.54.6"},"reference-count":31,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2013,9,9]],"date-time":"2013-09-09T00:00:00Z","timestamp":1378684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:p>A reference genotyping laboratory was established in 2000 at Queen's University, Kingston, to provide genetic testing for Hemophilia A (HA) and B (HB) and create a Canadian mutation database. Canadian hemophilia treatment centers and genetics clinics provided DNA and clinical information from November 2000 to March 2011. The factor VIII (F8) gene was analyzed in 1,177 patients (47% of HA population) and 787 female family members and the factor IX (F9) gene in 267 patients (47% of HB population) and 123 female family members, using Southern Blot, PCR, conformation sensitive gel electrophoresis, and\/or direct sequencing. The mutation detection rates for HA and HB were 91% and 94%, respectively. 380 different F8 mutations were identified: inversions of intron 22 and intron 1, 229 missense, 45 nonsense, eight deletions, 70 frameshifts, 25 splice site, and one compound mutation with a splice site and intron 1 inversion. Of these mutations, 228 were novel to the Hemophilia A Database (HADB, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/hadb.org.uk\/\">http:\/\/hadb.org.uk\/<\/jats:ext-link>). A total 125 different F9 mutations were identified: 80 missense, 12 frameshift, 12 splice site, nine nonsense and seven promoter mutations, three large deletions, and two compound mutations with both missense and nonsense changes. Of these mutations, 36 were novel to the International Haemophilia B Mutation database (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.kcl.ac.uk\/ip\/petergreen\/haemBdatabase.html\">http:\/\/www.kcl.ac.uk\/ip\/petergreen\/haemBdatabase.html<\/jats:ext-link>). The Canadian F8 and F9 mutation database reflects the allelic heterogeneity of HA and HB, and is similar to previously described populations. This report represents the largest and longest duration experience of a national hemophilia genotyping program documented, to date. Am. J. Hematol. 88:1030\u20131034, 2013. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.23557","type":"journal-article","created":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T19:15:51Z","timestamp":1375384551000},"page":"1030-1034","source":"Crossref","is-referenced-by-count":25,"title":["The Canadian \u201cNational Program for hemophilia mutation testing\u201d database: A ten\u2010year review"],"prefix":"10.1002","volume":"88","author":[{"given":"Rydz","family":"Natalia","sequence":"first","affiliation":[{"name":"Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leggo","family":"Jayne","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinlin","family":"Shawn","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular 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