{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T16:07:50Z","timestamp":1765728470637},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,6,29]],"date-time":"2012-06-29T00:00:00Z","timestamp":1340928000000},"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":[[2012,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Haemophilia A (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) is an X\u2010linked recessive bleeding disorder caused by defects in the <jats:italic>F8<\/jats:italic> gene encoding the coagulation factor VIII. Mutation analysis in <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> is important to confirm the diagnosis, genotype\u2010phenotype correlations and for genetic counselling and family study. The aim of this study was to detect causative mutations of <jats:italic>F8<\/jats:italic> in severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> patients in Korea and to correlate the mutation type with the risk of inhibitor development. A total of 100 unrelated Korean patients with severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> were enrolled for this study. The Nijeman modification of the Bethesda assay was used to determine the presence of inhibitor. Molecular analysis of <jats:italic>F8<\/jats:italic> was performed using a combination of molecular techniques, including long\u2010distance polymerase chain reaction, direct sequencing and multiplex ligation\u2010dependent probe amplification (<jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content>). We identified causative mutations in 98% of severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content> patients (98\/100). Inv22 and Inv1 mutations were detected in 30 patients and one patient, respectively. A total of 59 unique mutations were identified in 69 non\u2010inversion patients, including 24 novel mutations. The overall prevalence of inhibitor was 26%. Inhibitor risk was highest in patients with large deletion mutations identified using <jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content> (100%). Among those with point mutations, the prevalence of inhibitor was highest when the mutation occurred in the <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3 and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>2 domains (60% and 50%, respectively). The molecular diagnostic strategy involving multiplex <jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, sequencing and dosage analyses identified causative mutations in most cases of severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>. The high inhibitor risk was associated with large deletion mutations and point mutations in <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>3 and <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>2 domains.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2012.02895.x","type":"journal-article","created":{"date-parts":[[2012,6,29]],"date-time":"2012-06-29T10:01:53Z","timestamp":1340964113000},"page":"1008-1013","source":"Crossref","is-referenced-by-count":12,"title":["Mutation spectrum and inhibitor risk in 100 <scp>K<\/scp>orean patients with severe haemophilia <scp>A<\/scp>"],"prefix":"10.1111","volume":"18","author":[{"given":"H.\u2010J.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine &amp; Genetics Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010S.","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine &amp; Genetics Samsung Medical Center Sungkyunkwan University School of Medicine  Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. 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