Anti-FGA monoclonal antibody, clone DD1

Afibrinogenemia represents the rarest form of fibrinogen deficiency. Causative missense mutations occur rarely and may improve the understanding of fibrinogen structure and function. Patients and methods: The propositus was a 26-year-old Argentinian with afibrinogenemia. FGA, FGB and FGG exons and flanking regions were screened by sequencing and the mutant protein was analyzed in silico. Results: A novel missense mutation in the FGB gene (Bbeta Gly272Arg, p.Gly302Arg) was identified. In silico analysis revealed its location in a highly conserved region, which preserves the core fold of the C-terminal beta chain and is important for proper secretion. A substitution by a positively charged large Arg residue in this area would most likely disturb the core fold by additional interactions with adjacent residues (p.Asp291, p.Asp297, p.Asp311), or by forming of non-native interactions with other proteins, thereby hindering the action of molecular chaperones. Both alternatives would disturb the regular secretion of the beta-chain. Conclusions: The novel missense mutation in the FGB gene causes afibrinogenemia most probably by affecting the secretion of the fibrinogen beta-chain.

Objectives: Congenital dysfibrinogenemia is a rare hereditary disease characterized by normal antigen level but lower function level of fibrinogen. Patients with congenital dysfibrinogenemia usually present as bleeding and/or thrombotic events. In this study, we explored the genetic abnormality and clinical treatment of a Chinese family with dysfibrinogenemia. Methods: This study was conducted in Jan 2015 to Jan 2016 in the Second Medical College (Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong Province, P.R. China. Coagulation function test were used to screen patients in this family. For all family members, DNA from peripheral blood was isolated. Whole-genome exon sequencing was carried out to screen possible mutations. And sanger sequencing was employed to further confirm the mutation in patients. Results: The proband is a woman who had anemia and increased menstruation. Hypofibrinogenemia was found after admission. However, a pulmonary embolism occurred after the fibrinogen replacement treatment. Whole exon sequencing was conducted afterward. A candidate mutation in FGA gene (c.103C>A) was identified and validated in the woman and in two siblings. Conclusion: From this case, we learned that1) point mutation of c.103C>A is the pathogenesis for congenital dysfibrinogemia in this family; 2) thromboprophylaxis should always be in consideration when fibrinogen replacement is conducted. Prospective studies are needed to determine the best fibrinogen replacement strategy in order to achieve adequate hemostasis while minimize risk of thrombosis.