{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T18:09:25Z","timestamp":1774548565393,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Health of the Czech Republic","award":["00023736"],"award-info":[{"award-number":["00023736"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital fibrinogen disorders are caused by mutations in genes coding for fibrinogen and may lead to various clinical phenotypes. Here, we present a functional and structural analysis of 4 novel variants located in the FGB gene coding for fibrinogen B\u03b2 chain-heterozygous missense B\u03b2Y416C and B\u03b2A68S, homozygous nonsense B\u03b2Y345*, and heterozygous nonsense B\u03b2W403* mutations. The cases were identified by coagulation screening tests and further investigated by various methods. Fibrin polymerization had abnormal development with decreased maximal absorbance in all patients. Plasmin-induced fibrin degradation revealed different lytic phases of B\u03b2Y416C and B\u03b2W403* than those of the control. Fibrinopeptide cleavage measured by reverse phase high pressure liquid chromatography of B\u03b2A68S showed impaired release of fibrinopeptide B. Morphological properties, studied through scanning electron microscopy, differed significantly in the fiber thickness of B\u03b2Y416C, B\u03b2A68S, and B\u03b2W403*, and in the fiber density of B\u03b2Y416C and B\u03b2W403*. Finally, homology modeling of B\u03b2A68S showed that mutation caused negligible alternations in the protein structure. In conclusion, all mutations altered the correct fibrinogen function or structure that led to congenital fibrinogen disorders.<\/jats:p>","DOI":"10.3390\/ijms23020721","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T17:42:25Z","timestamp":1641836545000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Structural and Functional Characterization of Four Novel Fibrinogen Mutations in FGB Causing Congenital Fibrinogen Disorder"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-5967","authenticated-orcid":false,"given":"Eli\u0161ka","family":"Ceznerov\u00e1","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"},{"name":"Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0337-8204","authenticated-orcid":false,"given":"Ji\u0159ina","family":"Kaufmanov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, University of Chemistry and Technology Prague, Technick\u00e1 5, 16628 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3337-321X","authenticated-orcid":false,"given":"\u017dofie","family":"Sovov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5964-0526","authenticated-orcid":false,"given":"Jana","family":"\u0160tikarov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Lou\u017eil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Kotl\u00edn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-9718","authenticated-orcid":false,"given":"Ji\u0159\u00ed","family":"Suttnar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 2094\/1, 12800 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0167-7306(08)60053-8","article-title":"Chapter 7 Fibrinogen, fibrin and factor XIII","volume":"13","author":"Henschen","year":"1986","journal-title":"New Compr. 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