The β-Chain Mutation p.Arg17Stop Impairs Fibrinogen Synthesis and Secretion: A Nonsense Mutation Associated With Hypofibrinogenemia

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis Pub Date : 2024-12-12 DOI:10.1002/jcla.25123

Chen Qian, Chaoyu Huang, Qinghui Luo, Kaili Qin, Yangyang Wu, Lin Liao, Qian Zhang, Liqun Xiang, Jie Yan

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Abstract

Background

Congenital hypofibrinogenemia, a quantitative fibrinogen disorder, is characterized by abnormally low levels of both functional and antigen fibrinogen. We identified a heterozygous nonsense mutation, p.Arg17Stop, in the fibrinogen Bβ chain of a three-month-old female infant.

Methods

Coagulation testing, gene analysis, in vitro plasmid construction, and functional analyses were conducted to investigate the underlying pathogenic mechanisms.

Results

Plasma fibrinogen levels showed decrease in the proband. DNA sequencing of the proband revealed a heterozygous point mutation (c.139C>T) in exon 2 of the FGB gene causing Arg → Stop substitution. Human Arg17 was found to be highly conserved. In vitro expression analyses indicated that the mutation impacts both the transcription and translation of the FGB gene, subsequently affecting the synthesis and secretion of fibrinogen.

Conclusions

The p.Arg17Stop mutation in the fibrinogen Bβ chain disrupts fibrinogen production and secretion, contributing to hypofibrinogenemia.

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来源期刊

Journal of Clinical Laboratory Analysis 医学-医学实验技术

CiteScore

5.60

自引率

7.40%

发文量

584

审稿时长

6-12 weeks

期刊介绍： Journal of Clinical Laboratory Analysis publishes original articles on newly developing modes of technology and laboratory assays, with emphasis on their application in current and future clinical laboratory testing. This includes reports from the following fields: immunochemistry and toxicology, hematology and hematopathology, immunopathology, molecular diagnostics, microbiology, genetic testing, immunohematology, and clinical chemistry.