{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:23:57Z","timestamp":1770135837798,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,1,20]],"date-time":"2016-01-20T00:00:00Z","timestamp":1453248000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["K2013\u201064X\u201022298\u201001\u201003"],"award-info":[{"award-number":["K2013\u201064X\u201022298\u201001\u201003"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Many newly diagnosed Swedish severe haemophilia A (<jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>) patients are sporadic cases. Some genotypically non\u2010carrier mothers have gone on to have two descendants with the same mutation, presumably because of mosaicism. Aims: To define the origin of mutation in sporadic cases of <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>, reveal possible sex\u2010specific differences in mutagenesis and identify potential mosaics among non\u2010carrier mothers. Method: Sanger sequencing characterized the mutations and microsatellite haplotyping determined the origin of the X chromosome carrying the mutation in 3 generations of 45 families with sporadic severe <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>. Droplet digital polymerase chain reaction (<jats:styled-content style=\"fixed-case\">ddPCR<\/jats:styled-content>) was used in five cases to reveal that mosaicism mutations are not found on conventional <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing. Results: In 23 out of 45 families, the mother carried the mutation and in 5 out of 28 families, the grandmother was also a carrier. The X chromosome was of grandpaternal origin in 17 out of 23 cases. One of five tested mothers was a mosaic with a mutation frequency of 7%. Conclusion: In 40 out of 45 families, the sporadic case resulted from a mutation in the last two generations. In 82% (23\/28), the carrier mothers had a <jats:italic>de novo<\/jats:italic> mutation where the X chromosome was of paternal origin in 74% (17\/23). <jats:styled-content style=\"fixed-case\">ddPCR<\/jats:styled-content> is a potentially powerful and promising analysis for mosaicism in <jats:styled-content style=\"fixed-case\">HA<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cge.12709","type":"journal-article","created":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T09:35:55Z","timestamp":1449740155000},"page":"63-68","source":"Crossref","is-referenced-by-count":28,"title":["Origin of mutation in sporadic cases of severe haemophilia A in Sweden"],"prefix":"10.1111","volume":"90","author":[{"given":"A.","family":"M\u00e5rtensson","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Lund University  Malm\u00f6 Sweden"},{"name":"Department of Paediatrics and Malm\u00f6 Centre for Thrombosis and Haemostasis Sk\u00e5ne University Hospital, Lund 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