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.

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.

Objective To establish a method to quantify serum fat-soluble vitamins by liquid chromatography-tandem mass spectrome-try and evaluate their performance in preliminary clinical application.Methods The contents of fat-soluble vitamin in serum were quantified by liquid chromatography-tandem mass spectrometry.The samples were collected from 1 113 pregnant women from November 2022 to November 2023 at the Obstetrics Clinic of the First Affiliated Hospital of Soochow University.The method of liquid chromatog-raphy-tandem mass spectrometry for determination of fat-soluble vitamins in serum was validated referring to"Consensus of method de-velopment and validation of liquid chromatography-tandem mass spectrometry in clinical laboratories".Results The linear ranges of vitamin A,E,D2,D3 and K1 in serum were from 40 to 4 000 ng/mL,0.5 to 50 μg/mL,2 to 200 ng/mL,5 to 250 ng/mL and 0.1 to 10 ng/mL,respectively.The detectable limit was 2.50 ng/mL,0.10 ng/mL,0.40 ng/mL,1.00 ng/mL and 0.02 ng/mL,respec-tively.The limit of quantitation was 10.00 ng/mL,0.50 ng/mL,1.00 ng/mL,5.00 ng/mL and 0.10 ng/mL,respectively.The intra-batch coefficient of variation(CV)and inter-batch CV were all less than 15％.The rate of recovery was 91.25％to 107.18％,90.00％to 105.51％,92.88％to 107.87％,93.36％to 107.40％and 90.20％to 104.40％,respectively.The various fat-soluble vitamins in ser-um remained stable within 7 days under-20 ℃.The levels of fat-soluble vitamins in serum of pregnant women were detected by liquid chromatography-tandem mass spectrometry.There were significant differences of the levels and distributions for various fat-soluble vita-mins in the pregnant women in different age groups(P＜0.05),and the levels of fat-soluble vitamins gradually increased with the age.Conclusion The basic performance of the liquid chromatography-tandem mass spectrometry verified in this experiment was in line with the evaluation criteria,thus it should be highly sensitive and accurate for analyzing the contents of various fat-soluble vitamins in serum.