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DOI: 10.1055/s-0040-1714100
Genotype–Phenotype Relationships in a Large French Cohort of Subjects with Inherited Protein C Deficiency
Funding This study was supported in part by a DHOS program “Soutien financier en faveur des laboratoires pratiquant le diagnostic par génétique moléculaire des maladies rares.”![](https://www.thieme-connect.de/media/10.1055-s-00035024/202009/lookinside/thumbnails/10-1055-s-0040-1714100_200025-1.jpg)
Abstract
Inherited protein C (PC) deficiency caused by mutations in the PROC gene is a well-known risk factor for venous thromboembolism. Few studies have investigated the relationship between PROC genotype and plasma or clinical phenotypes. We addressed this issue in a large retrospective cohort of 1,115 heterozygous carriers of 226 PROC pathogenic or likely pathogenic mutations. Mutations were classified in three categories according to their observed or presumed association with type I, type IIa, or type IIb PC deficiency. The study population comprised 876 carriers of type I category mutations, 55 carriers of type IIa category mutations, and 184 carriers of type IIb category mutations. PC anticoagulant activity significantly influenced risk of first venous thrombosis (p trend < 10−4). No influence of mutation category on risk of whole or unprovoked thrombotic events was observed. Both PC anticoagulant activity and genotype significantly influenced risk of venous thrombosis. Effect of detrimental mutations on plasma phenotype was ambiguous in several carriers, whatever the mutation category. Altogether, our findings confirm that diagnosing PC inherited deficiency based on plasma measurement may be difficult but show that diagnosis can be improved by PROC genotyping.
Publikationsverlauf
Eingereicht: 20. Januar 2020
Angenommen: 30. Mai 2020
Artikel online veröffentlicht:
27. Juli 2020
© 2020. Thieme. All rights reserved.
Georg Thieme Verlag KG
Stuttgart · New York
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