Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia

Article Article scientifique Lettre Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia eng 2021 author Bartolo Raquel 940815 author Arbez Maxime 836990 author Ferreira Vilar Da Silva Rui Filipe 843527 author Szanto Timea author Lehtinen Elina author Trillot Nathalie author Rauch Antoine author Casini Alessandro 0000-0001-7910-933X 510964 author Neerman Arbez Marguerite 0000-0002-9351-4195 27647 5-8 10.1016/j.thromres.2021.07.013 34352655 0049-3848 This study describes the identification of two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency. Modelling of the impact of the mutations predict that these single amino acid substitutions are sufficient to abolish secretion of the mutant chains into the circulation, resulting in low fibrinogen levels in the patients. In addition, whole exome sequencing identified genetic modifiers for both patients which could contribute to the patients' global hemostatic function. Our results yield clinically relevant information for the personalised management of patients and eventually precision medicine for fibrinogen disorders. Dewey 616 Dewey 576.5 Swiss National Science Foundation Molecular mechanisms and clinical consequences of variable fibrinogen levels 172864 CH Projects Swiss National Science Foundation Molecular mechanisms and phenotypic consequences of variable fibrinogen levels 152633 CH Projects 135 Département de médecine génétique et développement 21D 56 Département de médecine 221 false 258 Recherche translationnelle : anomalies de l'hémostase et thromboses 504 1407 Fibrinogène et structure du caillot 1045 Thrombosis Research 206 3c3df21e-5dbb-4647-9b2f-3e17eaed6561 Article (Accepted version) Public BartoloThormbRes.pdf 306302 application/pdf Restricted 2023-01-01 33b66027-d140-4d7d-8dec-8cdf6227fa62 Supplemental data Restricted 1-s2.0-S0049384821004060-mmc1.docx 38462 application/vnd.openxmlformats-officedocument.wordprocessingml.document openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement Faculté de médecine / Section de médecine clinique / Département de médecine

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Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia	Thrombosis Research			2021	220	277

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Bartolo, Raquel