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Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency

Coagulation factor VII (proconvertin) is one of the proteins starting the blood coagulation cascade. Plasma FVII concentration is regulated by different factors. A low level of FVII could also be a result of FVII deficiency (MIM# 227500), the rare autosomal recessive inherited disease caused by path...

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Autores principales: Pshenichnikova, Olesya, Selivanova, Daria, Shchemeleva, Ekaterina, Abramova, Tatiana, Zozulya, Nadezhda, Surin, Vadim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531009/
https://www.ncbi.nlm.nih.gov/pubmed/37761907
http://dx.doi.org/10.3390/genes14091767
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author Pshenichnikova, Olesya
Selivanova, Daria
Shchemeleva, Ekaterina
Abramova, Tatiana
Zozulya, Nadezhda
Surin, Vadim
author_facet Pshenichnikova, Olesya
Selivanova, Daria
Shchemeleva, Ekaterina
Abramova, Tatiana
Zozulya, Nadezhda
Surin, Vadim
author_sort Pshenichnikova, Olesya
collection PubMed
description Coagulation factor VII (proconvertin) is one of the proteins starting the blood coagulation cascade. Plasma FVII concentration is regulated by different factors. A low level of FVII could also be a result of FVII deficiency (MIM# 227500), the rare autosomal recessive inherited disease caused by pathogenic variants in the F7 gene. The aim of this study was to describe a mutation spectrum of the F7 gene and genotype–phenotype relationship in patients with FVII deficiency in Russia for the first time. We studied the primary structure of the F7 gene of 54 unrelated patients with FVII deficiency by direct Sanger sequencing. Pathogenic variants in the F7 gene were detected in 37 (68.5%) of them. We identified 24 different mutations located mostly in the serine protease domain. Five pathogenic variants had never been reported before. A major mutation in the Russian population was c.1391delC (p. Pro464Hisfs*32), linked with rs36209567 and rs6046 functional polymorphisms, that is widely distributed in East Europe. As in other countries, the F7 genotypes poorly correlated with the severity of clinical manifestations but were quite well associated with FVII levels. Minor alleles of functional polymorphisms rs510335, rs5742910, rs561241, rs36209567, and rs6046 could also participate in the F7 genotype and influence FVII levels.
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spelling pubmed-105310092023-09-28 Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency Pshenichnikova, Olesya Selivanova, Daria Shchemeleva, Ekaterina Abramova, Tatiana Zozulya, Nadezhda Surin, Vadim Genes (Basel) Article Coagulation factor VII (proconvertin) is one of the proteins starting the blood coagulation cascade. Plasma FVII concentration is regulated by different factors. A low level of FVII could also be a result of FVII deficiency (MIM# 227500), the rare autosomal recessive inherited disease caused by pathogenic variants in the F7 gene. The aim of this study was to describe a mutation spectrum of the F7 gene and genotype–phenotype relationship in patients with FVII deficiency in Russia for the first time. We studied the primary structure of the F7 gene of 54 unrelated patients with FVII deficiency by direct Sanger sequencing. Pathogenic variants in the F7 gene were detected in 37 (68.5%) of them. We identified 24 different mutations located mostly in the serine protease domain. Five pathogenic variants had never been reported before. A major mutation in the Russian population was c.1391delC (p. Pro464Hisfs*32), linked with rs36209567 and rs6046 functional polymorphisms, that is widely distributed in East Europe. As in other countries, the F7 genotypes poorly correlated with the severity of clinical manifestations but were quite well associated with FVII levels. Minor alleles of functional polymorphisms rs510335, rs5742910, rs561241, rs36209567, and rs6046 could also participate in the F7 genotype and influence FVII levels. MDPI 2023-09-06 /pmc/articles/PMC10531009/ /pubmed/37761907 http://dx.doi.org/10.3390/genes14091767 Text en © 2023 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
Pshenichnikova, Olesya
Selivanova, Daria
Shchemeleva, Ekaterina
Abramova, Tatiana
Zozulya, Nadezhda
Surin, Vadim
Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title_full Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title_fullStr Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title_full_unstemmed Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title_short Molecular Genetic Analysis of Russian Patients with Coagulation Factor FVII Deficiency
title_sort molecular genetic analysis of russian patients with coagulation factor fvii deficiency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531009/
https://www.ncbi.nlm.nih.gov/pubmed/37761907
http://dx.doi.org/10.3390/genes14091767
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