{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T05:23:22Z","timestamp":1770441802805,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T00:00:00Z","timestamp":1411430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003398","name":"the Shanxi Scholarship Council of China","doi-asserted-by":"crossref","award":["2009 key7"],"award-info":[{"award-number":["2009 key7"]}],"id":[{"id":"10.13039\/501100003398","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81270587"],"award-info":[{"award-number":["81270587"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014207","name":"the National Public Health Grand Research Foundation","doi-asserted-by":"crossref","award":["201202017"],"award-info":[{"award-number":["201202017"]}],"id":[{"id":"10.13039\/501100014207","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Molecular characterization of haemophilia B (<jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>) at the factor <jats:styled-content style=\"fixed-case\">IX<\/jats:styled-content> gene (<jats:italic>F9<\/jats:italic>) is essential to establish diagnosis, confirm genotype\u2010phenotype correlations and to advise in genetic counselling. This study aimed to identify the causative mutations in 21 Chinese families with <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content> and to analyse the association of these mutations with clinical phenotype. Phenotypic analyses were performed using one\u2010stage assay for factor <jats:styled-content style=\"fixed-case\">IX<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>) activity (<jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>: C) and enzyme\u2010linked immunosorbent assay for <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content> antigen (<jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content>: Ag). Direct sequencing of the <jats:italic>F9<\/jats:italic> gene was carried out. For those suspected to have a large deletion, multiplex ligation\u2010dependent probe amplification (<jats:styled-content style=\"fixed-case\">MLPA<\/jats:styled-content>) was performed. Predicting the causal impact of new changes was studied by bioinformatics approaches. We also assessed the effect of the <jats:italic>F9<\/jats:italic> mutations on the <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content> protein structure and function. Causative mutations were detected in all study patients. There were 14 point mutations, three small deletions, one large deletion and one small in\u2010frame duplication that together comprised a total of 19 unique variants, of which five were novel. The structural and functional defects of novel missense and in\u2010frame deletion\/duplication mutations were demonstrated by bioinformatics approaches. The 12 missense mutations include five purely quantitative mutations, five predominantly qualitative abnormalities and two combined defects. Our data confirmed the genetic heterogeneity of the <jats:italic>F9<\/jats:italic> mutations. Quantitative missense mutations were found to be in different regions of precursor <jats:styled-content style=\"fixed-case\">FIX<\/jats:styled-content> compared with qualitative and combined ones.<\/jats:p>","DOI":"10.1111\/hae.12534","type":"journal-article","created":{"date-parts":[[2014,9,23]],"date-time":"2014-09-23T04:28:25Z","timestamp":1411446505000},"page":"859-865","source":"Crossref","is-referenced-by-count":6,"title":["Comprehensive analysis of phenotypes and genetics in 21 Chinese families with haemophilia B: characterization of five novel mutations"],"prefix":"10.1111","volume":"20","author":[{"given":"Z.\u2010P.","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Hematology the Second Hospital of Shanxi Medical University Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.\u2010H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology the Second Hospital of Shanxi Medical University 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