Abstract
Hypodysfibrinogenemia is the least frequently reported congenital fibrinogen disorder, characterized by both quantity and quality defects of fibrinogen. In this study, we investigated the molecular basis of hypodysfibrinogenemia in a Chinese family. Functional fibrinogen was measured by Clauss method, and the antigenic fibrinogen was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of fibrinogen genes (FGA, FGB and FGG) were analysed by direct DNA sequencing. To further evaluate its molecular and functional characterizations, fibrinogen was purified from the plasma of propositus, then SDS-PAGE, fibrin polymerization, clot lysis, and electron microscopy scanning were all performed. The propositus showed a slight decrease of immunologic fibrinogen (1.52 g/L) but dramatically reduced functional fibrinogen (0.3 g/L). DNA sequencing revealed a novel heterozygous CCTTTGATG deletion in the exon 8 of FGG, leading to the deletion of Ala289, Phe290, and Asp291 in fibrinogen γ-chain. The polymerization of the fibrinogen from the propositus was markedly impaired, with prolonged lag period and decreased final turbidity. The fibrinogen clottability showed a reduced fraction of participating clot formation. While...Continue Reading
References
Oct 12, 1978·Nature·B BlombäckL Therkildsen
Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·J A KantG R Crabtree
Jan 1, 1984·Annual Review of Biochemistry·R F Doolittle
Oct 23, 1997·Nature·G SpraggonR F Doolittle
Jul 20, 2001·Annals of the New York Academy of Sciences·M W MosessonD A Meh
Jan 5, 2002·Biochimica Et Biophysica Acta·S O BrennanP M George
Dec 8, 2004·Thrombosis and Haemostasis·Amy DearPeter M George
Dec 23, 2004·Journal of Thrombosis and Haemostasis : JTH·A DearP M George
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·M W Mosesson
Feb 21, 2009·Haematologica·Stephen O BrennanAnna Ruskova
Oct 8, 2009·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Yuka KamijyoNobuo Okumura
Sep 2, 2010·Thrombosis and Haemostasis·Silja VorjohannMarguerite Neerman-Arbez
Jan 12, 2013·Blood·John W Weisel, Rustem I Litvinov
Jul 16, 2013·Seminars in Thrombosis and Hemostasis·Philippe de MoerlooseMarguerite Neerman-Arbez
Dec 18, 2013·The Journal of Biological Chemistry·Nataly P PodolnikovaTatiana P Ugarova
Feb 18, 2017·Journal of Thrombosis and Haemostasis : JTH·A CasiniP de Moerloose
Jun 9, 2017·Haemophilia : the Official Journal of the World Federation of Hemophilia·Y AmriN E H Toumi