Analysis of an Inherited Dysfibrinogenemia Pedigree Associated with a Heterozygous Mutation in the FGA Gene

Abstract

Objective: This article aims to analyze the phenotype and genotype of an inherited dysfibrinogenemia pedigree associated with a heterozygous mutation in the FGA gene, and to investigate the pathogenesis of this disease.

Clinical presentation: The proband of interest is a 29-year-old woman. She was in her 37 weeks of gestation. Routine coagulation tests showed low fibrinogen activity (0.91 g/L; normal range: 2.0-4.0 g/L) and normal fibrinogen antigen (FIB:Ag) level (2.09 g/L; normal range: 2.0-4.0 g/L).

Techniques: The prothrombin time, activated partial thromboplastin time, thrombin time, and activity of plasma fibrinogen (FIB:C) were detected by the one-stage clotting method. The FIB:Ag, D-dimer, and fibrinogen degradation products were tested by the immunoturbidimetry method. To identify the novel missense mutation, fibrinogen gene sequencing and molecular modeling were performed. We used ClustalX-2.1-win and online bioinformatic software to analyze the conservation and possible effect of the amino acid substitution on fibrinogen.

Results: Phenotypic analysis revealed that the FIB:C of the proband was significantly reduced while the FIB:Ag was normal. Sequencing analysis detected a heterozygous C.2185G > A point mutation in the FGA gene (AαGlu710Lys). Bioinformatic and modeling analyses indicated that the mutation probably caused harmful effects on fibrinogen.

Conclusion: The heterozygous mutation of Glu710Lys in the FGA gene was identified that could cause the reduction of the FIB structure stability and result in the dysfibrinogenemia.