{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:12:15Z","timestamp":1789193535780,"version":"build-2803163510"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82430010"],"award-info":[{"award-number":["82430010"]}],"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":["82470147"],"award-info":[{"award-number":["82470147"]}],"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":["82470138"],"award-info":[{"award-number":["82470138"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2507803"],"award-info":[{"award-number":["2023YFC2507803"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"Summary<\/jats:title>\n \n Congenital factor XII (FXII) deficiency is a rare disorder resulting from\n F12<\/jats:italic>\n gene mutations and its precise contribution to thrombotic or haemorrhagic risk has yet to be established. We identified the same mutation of the\n F12<\/jats:italic>\n gene across five pedigrees, yet the clinical manifestations varied markedly, ranging from asymptomatic to thrombotic and haemorrhagic phenotypes. Haematological assessments and deoxyribonucleic acid sequencing were conducted in five pedigrees. All five probands displayed prolonged activated partial thromboplastin time, markedly reduced FXII activity and an identical frameshift mutation in\n F12<\/jats:italic>\n (c.303_304delCA, p.H101Qfs*36), leading to the loss of functional domains. In Pedigree A, characterized by thrombotic clustering, thrombotic events were documented in 4 of 6 mutation carriers and 4 of 13 non\u2010carriers. In Pedigree B, the proband experienced bleeding events, and her father died of intracerebral haemorrhage. Probands C and D remained asymptomatic. Proband E was diagnosed with essential thrombocythaemia and thrombosis. Across all pedigrees, haemorrhagic or thrombotic events could be attributed to additional contributing factors. The identified\n apolipoprotein E<\/jats:italic>\n and\n butyrophilin subfamily 2 member A1<\/jats:italic>\n variants were consistently associated with thrombotic events in Pedigree A. This\n F12<\/jats:italic>\n variant does not appear to independently drive pathological coagulation phenotypes but may potentiate susceptibility to thrombosis in the presence of additional genetic or acquired risk factors.\n <\/jats:p>","DOI":"10.1111\/bjh.70652","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T08:09:40Z","timestamp":1782893380000},"page":"1280-1290","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical heterogeneity in congenital factor\n XII<\/scp>\n deficiency: Coexisting risk factors in thrombotic and bleeding events"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9790-6836","authenticated-orcid":false,"given":"Xinmiao","family":"Qu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, 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