WANG Xiaoou,WANG Jinyuan,SHU Kuangyi, et al. Clinical characteristics and genotype analysis of a family with congenital dysfibrinogenemia due to a novel variant of FGG gene[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(5): 399-404.
Abstract：Objective: To analyze the clinical features and genotype of a family with congenital dysfibrinogenemia. Methods: Coagulation tests of the proband and his pedigree members were detected. The three fibrinogen genes (FGA, FGB and FGG) were amplified, then sequenced to find the varint. Three bioinformatics software (PolyPhen-2, PROVEAN and Mutation Taster) and PyMol were used to forecast the possible impact of the variant on the function of the protein. Conservation of the amino acids were analyzed by Clustal X. The effect of single point variants on protein stability was analyzed by I-Mutant Suite. The coagulation function of proband and his predigree members with thrombelastography (TEG) was evaluated. Results: The antigen of fibrinogen (Fg:Ag) of the proband in plasma was normal (3.20 g/L), but the activity (Fg:C) was significantly decreased (0.91 g/L). Genetic analysis revealed a heterozygous c.1133G>A mutation in the exon 9 of FGG, which resulted in p.Gly378Asp substitution. Family studies revealed that the mother and brother bear the same variant. All bioinformatics software that were used showed the variant could affect the function of Fg. Clustal X software showed that Gly378 was highly conserved among homologous species. The results of TEG indicated that the fibrinogen function of three members carrying the c.1133G>A mutation decreased. Conclusion: The proband with dysfibrinogenemia was caused by the mutation of γ chain Gly378Asp.
