Molecular Pathogenic Mechanism Study of Two Cases of Inherited Dysfibrinogenemia
10.19746/j.cnki.issn1009-2137.2025.01.027
- VernacularTitle:2例遗传性异常纤维蛋白原血症分子致病机制研究
- Author:
Min WANG
1
;
Tian-Ping CHEN
;
Ao-Shuang JIANG
;
Cheng-Lin ZHU
;
Nan WEI
;
Li-Juan ZHU
;
Li-Jun QU
;
Hong-Jun LIU
Author Information
1. 安徽省儿童医院血液肿瘤科,安徽 合肥 230022
- Publication Type:Journal Article
- Keywords:
FGA gene;
FGG gene;
inherited dysfibrinogenemia;
fibrinogen;
gene mutation
- From:
Journal of Experimental Hematology
2025;33(1):187-192
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze two families with inherited dysfibrinogenemia,and explore the molecular pathogenic mechanisms.Methods:The coagulation indexes of the probands and their family members were detected.The FGA,FGB,and FGG exons and their flanking sequences were amplified by PCR,and the mutation sites were identified by sequencing.SIFT,PolyPhen2,LRT,ReVe,MutationTaster,phyloP,and phastCons bioinformatics software were used to predict the functional impact of the mutation sites.Protein structure and amino acid conservation analysis of the variant were conducted using PyMOL and Clustal X software.Results:The thrombin time(TT)of the proband in family 1 was prolonged to 37.00 s,and Fg:C decreased to 0.52 g/L.The TT of the proband in family 2 was 20.30 s,and Fg:C was 1.00 g/L,which was lower than the normal range.Genetic analysis revealed that the proband in family 1 had a heterozygous mutation c.80T＞C in FGA,resulting in the substitution of phenylalanine 27 with serine(Phe27Ser).The proband in family 2 had a heterozygous mutation c.1007T＞A in FGG,resulting in the substitution of methionine 336 with lysine(Met336Lys).Bioinformatics software prediction analysis indicated that both mutations were deleterious variants.PyMOL mutation models revealed that the Aα chain mutation(Phe27Ser)in family 1 and y chain mutation(Met336Lys)in family 2 resulted in alterations in spatial structure and reduced protein stability.Clustal X results showed that both Aα Phe27 and γMet336 were highly conserved across homologous species.Conclusion:Heterozygous mutations of FGA gene c.80T＞C and FGG gene c.1007T＞A are both pathogenic variants,causing inherited dysfibrinogenemia.
