{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:52:35Z","timestamp":1792785155064,"version":"4.5.0"},"reference-count":29,"publisher":"Georg Thieme Verlag KG","funder":[{"name":"Self-financing Scientific Research Subject of Guangxi Health Department","award":["Z-A20241075"],"award-info":[{"award-number":["Z-A20241075"]}]},{"name":"Open Project of Key Laboratory of Hematology, Guangxi Medical University","award":["GXHKL202308"],"award-info":[{"award-number":["GXHKL202308"]}],"id":[{"id":"https:\/\/ror.org\/03dveyr97","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hamostaseologie"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background Fibrinogen, encoded by FGA, FGB, and FGG, is essential for blood coagulation. Mutations in these genes cause congenital fibrinogen disorders, leading to bleeding and thrombotic complications. The B\u03b2 chain is the rate-limiting component in fibrinogen production, and its C-terminal region is essential for assembly and secretion. However, the pathogenic mechanism of missense mutations in the FGB gene remains to be fully elucidated.<\/jats:p>\n                  <jats:p>Objective This study aimed to analyze the genotype and phenotype of a pedigree with hereditary hypofibrinogenemia and to preliminarily elucidate the potential pathogenic mechanism.<\/jats:p>\n                  <jats:p>Methods Fibrinogen levels were measured using the Clauss and PT-derived methods. DNA sequence analysis was performed to identify the mutation. Conservation and protein structural modeling analyses were performed using online bioinformatics tools. The pathogenicity of the variant was assessed according to the ACMG\/AMP guidelines.<\/jats:p>\n                  <jats:p>Results The fibrinogen level of the proband was 0.74 g\/L. Thromboelastography (TEG) showed that the proband\u2019s clot kinetics time (K time) was 4.4 min (prolonged), thrombus generation angle (\u03b1 angle) was 42.6\u00b0 (decreased), and clotting index (CI) was \u22124.8 (decreased). Genetic analysis revealed a heterozygous c.923C &gt; A (p.Thr308Asn) mutation in FGB gene. Bioinformatics and modeling analysis suggested that the missense mutation may have a deleterious effect on fibrinogen. The variant was classified as likely pathogenic based on the ACMG\/AMP guidelines.<\/jats:p>\n                  <jats:p>Conclusion The c.923C &gt; A(p.Thr308Asn) mutation in exon 6 of the FGB gene may be responsible for the reduced fibrinogen level observed in this pedigree. To our knowledge, this point mutation is reported for the first time.<\/jats:p>","DOI":"10.1055\/a-2937-0837","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:11:01Z","timestamp":1787785861000},"source":"Crossref","is-referenced-by-count":0,"title":["A novel Mutation p.Thr308Asn in the Snout-like Region of the Fibrinogen B\u03b2 Chain: Analysis of the Pathogenic Mechanism of Hereditary Hypofibrinogenemia"],"prefix":"10.1055","author":[{"given":"Jinxiong","family":"Jiang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University, Guangxi, China","place":["Nanning"],"department":["Department of Clinical Laboratory"]},{"name":"Key Laboratory of Clinical Laboratory Medicine of Guangxi, Guangxi, China","place":["Nanning"],"department":["Department of 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Fourth People\u2019s Hospital of Nanning, Guangxi, China","place":["Nanning"],"department":["Department of Clinical Laboratory"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxin","family":"Yu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University, Guangxi, China","place":["Nanning"],"department":["Department of Clinical Laboratory"]},{"name":"Key Laboratory of Clinical Laboratory Medicine of Guangxi, Guangxi, China","place":["Nanning"],"department":["Department of Education"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufeng","family":"Gan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guangxi Medical University, Guangxi, China","place":["Nanning"],"department":["Department of Clinical Laboratory"]},{"name":"Key Laboratory of Clinical Laboratory Medicine of Guangxi, Guangxi, China","place":["Nanning"],"department":["Department of 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Spraggon","year":"1997","journal-title":"Nature"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.blre.2014.09.003","article-title":"Fibrinolysis and the control of blood coagulation","volume":"29","author":"J C Chapin","year":"2015","journal-title":"Blood Rev"},{"issue":"08","key":"ref3","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/MBC.0000000000000948","article-title":"A novel heterozygous mutation (\u03b3IIe367Thr) causes congenital dysfibrinogenemia in a Chinese family","volume":"31","author":"S Luo","year":"2020","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"04","key":"ref4","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1055\/s-0036-1571340","article-title":"Laboratory and genetic investigation of mutations accounting for congenital fibrinogen disorders","volume":"42","author":"M Neerman-Arbez","year":"2016","journal-title":"Semin Thromb 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B\u03b2255 Arg\u2192his (fibrinogen Merivale)","volume":"1645","author":"G J Maghzal","year":"2003","journal-title":"Biochim Biophys Acta, Proteins Proteomics"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1055\/s-0037-1615603","article-title":"Hypofibrinogenemia due to novel 316 asp \u2192 Tyr substitution in the fibrinogen Bbeta chain","volume":"85","author":"S O Brennan","year":"2001","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref19","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.thromres.2014.01.022","article-title":"FGB mutations leading to congenital quantitative fibrinogen deficiencies: an update and report of four novel mutations","volume":"133","author":"A Casini","year":"2014","journal-title":"Thromb Res"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.thromres.2021.07.013","article-title":"Novel missense mutations affecting the structure of the conserved fibrinogen b\u03b2 C-terminal domain cause congenital hypofibrinogenemia","volume":"206","author":"R B\u00e1rtolo","year":"2021","journal-title":"Thromb Res"},{"issue":"10","key":"ref21","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1055\/a-2514-7520","article-title":"Clinical and genetic characterization of 51 patients with congenital fibrinogen disorders from China","volume":"125","author":"Y Cai","year":"2025","journal-title":"Thromb Haemost"},{"issue":"06","key":"ref22","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1182\/bloodadvances.2023012186","article-title":"Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the prospective rare bleeding disorders database","volume":"8","author":"S Mohsenian","year":"2024","journal-title":"Blood Adv"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S0002-9440(10)64923-1","article-title":"Fibrinogen stabilizes placental-maternal attachment during embryonic development in the mouse","volume":"160","author":"T Iwaki","year":"2002","journal-title":"Am J Pathol"},{"key":"ref24","first-page":"37","article-title":"Studies on the role of adhesive proteins in maintaining pregnancy","volume":"50","author":"T Asahina","year":"2004","journal-title":"Horm Res"},{"issue":"04","key":"ref25","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.thromres.2013.08.023","article-title":"The role of fibrin matrices and tissue factor in early-term trophoblast proliferation and spreading","volume":"132","author":"A Snir","year":"2013","journal-title":"Thromb Res"},{"issue":"06","key":"ref26","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/j.1365-2516.2008.01831.x","article-title":"Rare inherited disorders of fibrinogen","volume":"14","author":"S S Acharya","year":"2008","journal-title":"Haemophilia"},{"issue":"06","key":"ref27","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.siny.2011.07.006","article-title":"Management of pregnancy and delivery in women with inherited bleeding disorders","volume":"16","author":"F Peyvandi","year":"2011","journal-title":"Semin Fetal Neonatal Med"},{"issue":"03","key":"ref28","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1182\/blood-2014-06-582866","article-title":"Natural history of patients with congenital dysfibrinogenemia","volume":"125","author":"A Casini","year":"2015","journal-title":"Blood"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/S0049-3848(13)70004-5","article-title":"Epidemiology and treatment of congenital fibrinogen deficiency","volume":"130","author":"F Peyvandi","year":"2012","journal-title":"Thromb Res"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1055\/s-0036-1571339","article-title":"Clinical features and Management of Congenital Fibrinogen Deficiencies","volume":"42","author":"A Casini","year":"2016","journal-title":"Semin Thromb Hemost"}],"container-title":["H\u00e4mostaseologie"],"original-title":[],"language":"de","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2937-0837.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:56:51Z","timestamp":1791417411000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2937-0837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":29,"URL":"https:\/\/doi.org\/10.1055\/a-2937-0837","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0720-9355","2567-5761"],"issn-type":[{"value":"0720-9355","type":"print"},{"value":"2567-5761","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}