A novel missense mutation in the FGB gene (p.Gly302Arg) leading to afibrinogenemia Predicted structure and function consequences

作者：Ivaskevicius V^*; Ruehl H; Detarsio G; Biswas A; Gupta S; Davoli M; Quartara A; Perez S; Raviola M; Oldenburg J

来源：Hamostaseologie, 2016, 36(4A): S34-S37.

• Fibrinogen
• Afibrinogenemia
• bleeding
• FGA
• FGB
• FGG

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.

• 出版日期2016-11