• Yessine Amri, Choumous Kallel, Mariem Becheur, Rym Dabboubi, Moez Elloumi, Hatem Belaaj, Sami Kammoun, Taieb Messaoud, Philippe de Moerloose, and Nour El Houda Toumi.
• Hematology Laboratory, Bechir Hamza Children's Hospital, Tunis, Tunisia. Electronic address: amri.yessine@yahoo.com.
• Clin. Chim. Acta. 2016 Sep 1; 460: 55-62.

BackgroundCongenital disorders of fibrinogen are rare diseases resulting in the complete absence (afibrinogenemia), reduced concentration (hypofibrinogenemia) or altered function of circulating fibrinogen (dysfibrinogenemia). A combination of two different fibrinogen abnormalities with a significant functional and secretion defect (hypodysfibrinogenemia) reported in Tunisian family members, was investigated in this study.MethodsThe coagulation-related tests, kinetics of fibrin polymerization and lysis and fibrinogen analysis using gel electrophoresis were performed in the family members to characterize fibrinogen abnormalities. All exons including exon-intron boundaries of fibrinogen genes were screened by direct sequencing.ResultsMutational screening of the fibrinogen genes disclosed novel missense mutations, BβCys197Arg, in exon 4 of the fibrinogen Bβ-chain gene. After the loose of its partner in Bβ-chain, the γCys135 was probably disulfide-bridged to its corresponding Cys residue of another abnormal fibrinogen molecule, forming dimmer with an abnormal electrophoretic profile. Homozygous form carried by the proband found to be directly involved in the bleeding phenotype by affecting fibrin polymerization. In contrast, affected family members bearing the heterozygous mutation showed an impaired fibrin polymerization and fibrinolysis leading to thrombosis.ConclusionThese results suggest that this mutation could alter the extremely conserved conformations of fibrinogen D domain and D-D lateral regions on fibrin assembly.Copyright © 2016 Elsevier B.V. All rights reserved.

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