Clinical characteristics and molecular genetic analysis of a family with c.1001A>C mutation in the FGG gene of fibrinogen
10.13602/j.cnki.jcls.2025.07.06
- VernacularTitle:纤维蛋白原FGG基因c.1001A>C突变家系的临床特征及分子遗传学分析
- Author:
Hairong DING
1
;
Chen WANG
1
;
Dong ZHENG
1
;
Cifu QU
1
;
Jun QIU
1
Author Information
1. 苏州大学附属第一医院临床检测中心,江苏 苏州 215006
- Publication Type:Journal Article
- Keywords:
inherited fibrinogen disorders;
autosomal dominant inheritance;
FGG gene mutation;
protein spatial structure analysis
- From:
Chinese Journal of Clinical Laboratory Science
2025;43(7):514-519
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the coagulation abnormalities and molecular genetic characteristics of a family with asymptomatic inherited fibrinogen disorders(IFD).Methods The clinical data of a family with IFD,including 5 individuals from two generations,were collected.Their peripheral blood coagulation indicators were detected.The coding sequences of FGA,FGB and FGG genes were amplified by PCR and Sanger sequencing was used to identify the candidate variants,which were further validated in the family mem-bers.The bioinformatic software was used to analyze the pathogenicity and conservation of the missense mutation and its effect on the spatial structure and function of the protein.Results The IFD patients had significantly low fibrinogen antigen(Fg:Ag)concentration and fibrinogen coagulation(Fg:C)activity concentration as well as prolonged thrombin time(TT),while coagulation indicators of the unaffected relatives were normal.The results of Sanger sequencing showed that all IFD patients carried a heterozygous missense variant of c.1001A>C(p.Asn334Thr)in the FGG gene.The bioinformatic analysis suggested that Asn334Thr was a pathogenic variant,while homology analysis indicated that the Asn334 locus was highly conserved in evolution.The analysis of protein spatial structure showed that the Asn334Thr mutation altered hydrogen bonds between amino acids.Conclusion The heterozygous missense variant c.1001A>C(p.Asn334Thr)in the FGG gene may be the pathogenic cause of the proband.The finding enriches the spectrum of FGG gene mutations and provides experimental evidence for the genetic counseling of affected families.
