A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms

Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristic...

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Autores principales: Weronska, Anna, Potaczek, Daniel P., Oto, Julia, Medina, Pilar, Undas, Anetta, Wypasek, Ewa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141864/
https://www.ncbi.nlm.nih.gov/pubmed/35627118
http://dx.doi.org/10.3390/genes13050733
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author Weronska, Anna
Potaczek, Daniel P.
Oto, Julia
Medina, Pilar
Undas, Anetta
Wypasek, Ewa
author_facet Weronska, Anna
Potaczek, Daniel P.
Oto, Julia
Medina, Pilar
Undas, Anetta
Wypasek, Ewa
author_sort Weronska, Anna
collection PubMed
description Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristics, including long-term follow-up data and a deep mutational analysis of the PROC gene. Patients and Methods: Fourteen unrelated probands (mean ± SD age 43.8 ± 13.0 years) with suspicion of PC deficiency, who experienced thromboembolic events and a majority of whom received anticoagulants (92.8%), were screened for PROC mutations by sequencing the nine PROC exons and their flanking intron regions. Results: Ten probands (71.4%) had missense mutations, two patients (14.3%) carried nonsense variants, and the other two subjects (14.3%) had splice-site mutations, the latter including the c.401-1G>A variant, reported here for the very first time. The proband carrying the c.401-1A allele had a hepatic artery aneurysm with a highly positive family history of aneurysms and the absence of any mutations known to predispose to this vascular anomaly. Conclusion: A novel detrimental PROC mutation was identified in a family with aneurysms, which might suggest yet unclear links of thrombophilia to vascular anomalies, including aneurysms at atypical locations in women. The present case series also supports data indicating that novel oral anticoagulants (NOACs) are effective in PC deficient patients.
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spelling pubmed-91418642022-05-28 A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms Weronska, Anna Potaczek, Daniel P. Oto, Julia Medina, Pilar Undas, Anetta Wypasek, Ewa Genes (Basel) Article Objectives: Protein C (PC) deficiency is an inherited thrombophilia with a prevalence of 0.5% in the general population and 3% in subjects with a first-time deep vein thrombosis (DVT). Here we report a series of 14 PC-deficient Polish patients with comprehensive clinical and molecular characteristics, including long-term follow-up data and a deep mutational analysis of the PROC gene. Patients and Methods: Fourteen unrelated probands (mean ± SD age 43.8 ± 13.0 years) with suspicion of PC deficiency, who experienced thromboembolic events and a majority of whom received anticoagulants (92.8%), were screened for PROC mutations by sequencing the nine PROC exons and their flanking intron regions. Results: Ten probands (71.4%) had missense mutations, two patients (14.3%) carried nonsense variants, and the other two subjects (14.3%) had splice-site mutations, the latter including the c.401-1G>A variant, reported here for the very first time. The proband carrying the c.401-1A allele had a hepatic artery aneurysm with a highly positive family history of aneurysms and the absence of any mutations known to predispose to this vascular anomaly. Conclusion: A novel detrimental PROC mutation was identified in a family with aneurysms, which might suggest yet unclear links of thrombophilia to vascular anomalies, including aneurysms at atypical locations in women. The present case series also supports data indicating that novel oral anticoagulants (NOACs) are effective in PC deficient patients. MDPI 2022-04-22 /pmc/articles/PMC9141864/ /pubmed/35627118 http://dx.doi.org/10.3390/genes13050733 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Weronska, Anna
Potaczek, Daniel P.
Oto, Julia
Medina, Pilar
Undas, Anetta
Wypasek, Ewa
A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title_full A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title_fullStr A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title_full_unstemmed A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title_short A Series of 14 Polish Patients with Thrombotic Events and PC Deficiency-Novel c.401-1G>A PROC Gene Splice Site Mutation in a Patient with Aneurysms
title_sort series of 14 polish patients with thrombotic events and pc deficiency-novel c.401-1g>a proc gene splice site mutation in a patient with aneurysms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141864/
https://www.ncbi.nlm.nih.gov/pubmed/35627118
http://dx.doi.org/10.3390/genes13050733
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