{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T08:56:31Z","timestamp":1770454591461,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570114"],"award-info":[{"award-number":["81570114"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570115"],"award-info":[{"award-number":["81570115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Sporadic haemophilia B (HB) without obvious familial history poses challenges for genetic diagnosis and counselling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To identify the <jats:italic>F9<\/jats:italic> variants in sporadic HB patients and probe the origin of these de novo mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A total of 294 unrelated HB pedigrees sought genetic diagnosis were analysed in this single\u2010centre study. The <jats:italic>F9<\/jats:italic> gene was analysed by direct sequencing, and AccuCopy technique was adopted to screen for gene copy number variations. Six short tandem repeats approximal or within <jats:italic>F9<\/jats:italic> gene were applied for linkage analysis. Mosaicism of sequence variant was determined by ddNTP Primer Extension method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sporadic HB patients constituted 36% (61\/294) of cases enrolled in current study. The sporadic and familial HB patients shared similar spectrum of <jats:italic>F9<\/jats:italic> variants, with single nucleotide substitution as predominant form of disease\u2010causing mutation and no mutation prone hotspot sites, including CpG dinucleotide sequences, had been identified. Majority of the mothers of sporadic HB patients were <jats:italic>F9<\/jats:italic> mutation carriers (70%, 43\/61), and most of them (95%, 41\/43) had the inherited bleeding trait traced back to maternal grandfathers. Although most de novo mutations occur in germ cells, 2 maternal grandfathers, who had somatic mosaic mutations of <jats:italic>F9<\/jats:italic>, were also revealed to be the source of genetic variations identified in patients. In our cohort, FIX inhibitor incidence was 1%, developed only in patients carrying null mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The diversity of <jats:italic>F9<\/jats:italic> genetic variants and possible mosaicism of de novo mutation demand extensive study and more cautious in genetic counselling of sporadic HB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.13681","type":"journal-article","created":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T13:07:28Z","timestamp":1547644048000},"page":"316-323","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The characteristics and spectrum of <i>F9<\/i> mutations in Chinese sporadic haemophilia B pedigrees"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-1128","authenticated-orcid":false,"given":"Yeling","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Laboratory 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