Related Experiment Video
Updated: May 22, 2025
07:09
Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States
Published on: April 1, 2015
11.4K
Congenital Fibrinogen Deficiencies: Not So Rare.
Alexander Couzens1, Marguerite Neerman-Arbez1
1Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva and Institute of Genetics and Genomics in Geneva (iGE3), Geneva, Switzerland.
Hamostaseologie
|March 12, 2025
Summary
Congenital fibrinogen deficiencies (CFDs) are more common and genetically complex than previously thought. Updated estimates suggest recessive CFDs affect 29 per million and dominant CFDs up to 15,000 per million people.
Area of Science:
- Genetics
- Hematology
- Molecular Biology
Background:
- Congenital fibrinogen deficiencies (CFDs) were traditionally viewed as rare monogenic disorders.
- Emerging evidence suggests CFDs are more prevalent and genetically complex, involving multiple genes beyond FGB, FGA, and FGG.
- Patient symptoms like bleeding and thrombosis may stem from polygenic influences.
Purpose of the Study:
- To review recent advancements in understanding the genetic underpinnings of CFDs.
- To provide updated global prevalence estimates for CFDs using novel genetic datasets.
- To explore the genetic variability contributing to CFD phenotypes.
Main Methods:
- Literature review of recent advances in CFD genetics.
- Analysis of gnomAD v4.1.0. database (over 800,000 individuals).
- Estimation of CFD prevalence based on predicted deleterious variant frequencies in FGB, FGA, and FGG genes.
Main Results:
- Recessively inherited CFDs (homozygous genotypes) estimated at ~29 per million.
- Dominantly inherited CFDs (heterozygous genotypes) estimated up to ~15,000 per million.
- Increased prevalence estimates are linked to expanded and more diverse genetic data in gnomAD v4.1.0.
Conclusions:
- CFDs are more prevalent than previously recognized.
- Genetic complexity and broader variant spectrum contribute to CFD prevalence.
- Updated prevalence data are crucial for clinical understanding and management of CFDs.
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