{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:41:58Z","timestamp":1782949318990,"version":"3.54.5"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T00:00:00Z","timestamp":1448582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003252","name":"Lunds Universitet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Haemophilia B is caused by a heterogeneous spectrum of mutations. Mutation characterization is important in genetic counselling, prenatal diagnosis and to predict risk of inhibitor development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To study the mutation spectrum, frequency of unique recurrent mutations, genotype\u2013phenotype association and inhibitor development in a population\u2010based study of the complete Swedish haemophilia B population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included, facilitated by centralized <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> diagnostics, the complete registered Swedish haemophilia B population (113 families: 47 severe, 22 moderate and 44 mild), each represented by a single patient. Mutation characterization was performed by conventional sequencing of all exons and haplotyping by genotyping of single nucleotide variants and microsatellites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A mutation was found in every family: eight had large deletions, three had small deletions (&lt;10 base pair) and 102 had single base pair substitutions (69 missense, 26 nonsense, four splice site and three promoter). Ten novel mutations were found and were predicted to be deleterious. Sixteen mutations (one total gene deletion, 14 substitutions and one acceptor splice site) were present in more than one family. Of the single nucleotide mutations (37\/102), 36% arose at CpG sites. Haplotyping of families with identical mutations and present analyses showed that the frequency of unique mutations was at least 65%. Inhibitors developed in 9\/47 (19%) patients with severe haemophilia B.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The spectrum of haemophilia B mutations reveals at least 65% of the families carry a unique mutation, but with more inhibitor patients than reported internationally, probably as a result of many \u2018null\u2019 mutations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12854","type":"journal-article","created":{"date-parts":[[2015,11,27]],"date-time":"2015-11-27T06:34:39Z","timestamp":1448606079000},"page":"440-445","source":"Crossref","is-referenced-by-count":22,"title":["Mutation analysis of Swedish haemophilia B families \u2013 high frequency of unique mutations"],"prefix":"10.1111","volume":"22","author":[{"given":"A.","family":"M\u00e5rtensson","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Paediatrics and Malm\u00f6 Centre for Thrombosis and Haemostasis Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Letelier","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Paediatrics and Malm\u00f6 Centre for Thrombosis and Haemostasis Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Halld\u00e9n","sequence":"additional","affiliation":[{"name":"Biomedicine Kristianstad University Kristianstad Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ljung","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Lund University Malm\u00f6 Sweden"},{"name":"Department of Paediatrics and Malm\u00f6 Centre for Thrombosis and Haemostasis Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00335a049"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12276"},{"key":"e_1_2_10_4_1","unstructured":"Royal Free London NHS Foundation Trust.Factor IX variant database.London UK 2012. 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