{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T04:45:59Z","timestamp":1771994759617,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T00:00:00Z","timestamp":1595203200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Particular fibrinogen \u03b3 chain mutations occurring in the \u03b3-module induce changes that hamper \u03b3-\u03b3 dimerization and provoke intracellular aggregation of the mutant fibrinogen, defective export and plasma deficiency. The hepatic storage predisposes to the development of liver disease. This condition has been termed hereditary hypofibrinogenemia with hepatic storage (HHHS). So far, seven of such mutations in the fibrinogen \u03b3 chain have been detected. We are reporting on an additional mutation occurring in a 3.5-year-old Turkish child undergoing a needle liver biopsy because of the concomitance of transaminase elevation of unknown origin and low plasma fibrinogen level. The liver biopsy showed an intra-hepatocytic storage of fibrinogen. The molecular analysis of the three fibrinogen genes revealed a mutation (Fibrinogen Trabzon Thr371Ile) at exon 9 of the \u03b3 chain in the child and his father, while the mother and the brother were normal. Fibrinogen Trabzon represents a new fibrinogen \u03b3 chain mutation fulfilling the criteria for HHHS. Its occurrence in a Turkish child confirms that HHHS can present in early childhood and provides relevant epidemiological information on the worldwide distribution of the fibrinogen \u03b3 chain mutations causing this disease. By analyzing fibrinogen crystal structures and calculating the folding free energy change (\u0394\u0394G) to infer how the variants can affect the conformation and function, we propose a mechanism for the intracellular aggregation of Fibrinogen Trabzon and other \u03b3-module mutations causing HHHS.<\/jats:p>","DOI":"10.3390\/ijms21145139","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T10:59:38Z","timestamp":1595242778000},"page":"5139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Structural Characteristics in the \u03b3 Chain Variants Associated with Fibrinogen Storage Disease Suggest the Underlying Pathogenic Mechanism"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5142-8168","authenticated-orcid":false,"given":"Guven","family":"Burcu","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-849X","authenticated-orcid":false,"given":"Emanuele","family":"Bellacchio","sequence":"additional","affiliation":[{"name":"Area di Ricerca Genetica e Malattie Rare, Bambino Ges\u00f9 Children Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elif","family":"Sag","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alper Han","family":"Cebi","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismail","family":"Saygin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9226-369X","authenticated-orcid":false,"given":"Aysenur","family":"Bahadir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guldal","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Gazi University, Ankara 06170, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-5717","authenticated-orcid":false,"given":"Marialuisa","family":"Corbeddu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Bambino Ges\u00f9 Children Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4071-6129","authenticated-orcid":false,"given":"Murat","family":"Cakir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Karadeniz Technical University, Trabzon 61000, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Callea","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Histopathology, Catholic University and Bugando Medical Centre, Mwanza P.O. Box 1464, Tanzania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1749-6632.2001.tb03491.x","article-title":"The structure and biological features of fibrinogen and fibrin","volume":"936","author":"Mosesson","year":"2001","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_2","unstructured":"Mosesson, M.W. (2006). Hereditary fibrinogen abnormalities. Williams Hematology, Mac Grow-Hill. [7th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0002-9440(10)64530-0","article-title":"Fibrinogen Brescia. Fibrinogen brescia: Hepatic endoplasmic reticulum storage and hypofibrinogenemia because of a gamma284 Gly-->Arg mutation","volume":"157","author":"Brennan","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_4","unstructured":"Lowe, G.D.O. (1987). 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