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 Bβ chain-heterozygous missense BβY416C and BβA68S, homozygous nonsense BβY345*, and heterozygous nonsense BβW403* 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 BβY416C and BβW403* than those of the control. Fibrinopeptide cleavage measured by reverse phase high pressure liquid chromatography of BβA68S showed impaired release of fibrinopeptide B. Morphological properties, studied through scanning electron microscopy, differed significantly in the fiber thickness of BβY416C, BβA68S, and BβW403*, and in the fiber density of BβY416C and BβW403*. Finally, homology modeling of BβA68S 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.

• Keywords
• FGB, afibrinogenemia, congenital fibrinogen disorder, dysfibrinogenemia, functional assays, homology modeling, hypofibrinogenemia, scanning electron microscopy,
• MeSH
• Afibrinogenemia blood   diagnosis   genetics   MeSH
• Phenotype * MeSH
• Fibrinogen chemistry   genetics   metabolism   MeSH
• Genetic Predisposition to Disease * MeSH
• Genetic Association Studies MeSH
• Blood Coagulation MeSH
• Protein Conformation MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Models, Molecular MeSH
• Mutation * MeSH
• DNA Mutational Analysis MeSH
• Infant, Newborn MeSH
• Aged MeSH
• Blood Coagulation Tests MeSH
• Structure-Activity Relationship MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Infant, Newborn MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Names of Substances
• FGB protein, human MeSH Browser
• Fibrinogen MeSH