Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes
Background and Aims: Antithrombin (AT) is the most important physiological inhibitor in vivo, and coagulation factor II (FII) or prothrombin is a coagulation factor vital to life. The purpose of our research was to illustrate the connection between gene mutations and the corresponding deficiencies o...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.832582/full |
| _version_ | 1818355730954059776 |
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| author | Haiyue Zhang Yiling Hu Dongli Pan Yuehua Xv Weifeng Shen |
| author_facet | Haiyue Zhang Yiling Hu Dongli Pan Yuehua Xv Weifeng Shen |
| author_sort | Haiyue Zhang |
| collection | DOAJ |
| description | Background and Aims: Antithrombin (AT) is the most important physiological inhibitor in vivo, and coagulation factor II (FII) or prothrombin is a coagulation factor vital to life. The purpose of our research was to illustrate the connection between gene mutations and the corresponding deficiencies of AT and FII.Methods: Functional and molecular analyses were performed. The possible impact of the mutation was analyzed by online bioinformatics software. ClustalX-2.1-win and PyMol/Swiss-Pdb Viewer software were used for conservative analyses and to generate molecular graphic images, respectively.Results: The proband showed a lower limb venous thrombosis and acute pulmonary embolism infarction with reduced AT activity (50%). His mother, with subcutaneous ecchymosis, had reduced activities of AT and FII, of 44 and 5%, respectively. Molecular analysis showed that both the proband and his mother carried c.964A > T (p.Lys322stop) heterozygotes in SERPINC1. The difference was that his mother carried homozygous c.494C > T (p.Thr165Met) in F2, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein.Conclusion: This study identified a novel mutation of SERPINC1 and a missense mutation of F2, which may be the molecular mechanism leading to AT and FII deficiency in this family. It will help genetic diagnosis and counseling for thrombotic families. |
| first_indexed | 2024-12-13T19:45:58Z |
| format | Article |
| id | doaj.art-38388e67eeba4b43a7400c80d46a351e |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-13T19:45:58Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-38388e67eeba4b43a7400c80d46a351e2022-12-21T23:33:33ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.832582832582Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin HeterozygotesHaiyue ZhangYiling HuDongli PanYuehua XvWeifeng ShenBackground and Aims: Antithrombin (AT) is the most important physiological inhibitor in vivo, and coagulation factor II (FII) or prothrombin is a coagulation factor vital to life. The purpose of our research was to illustrate the connection between gene mutations and the corresponding deficiencies of AT and FII.Methods: Functional and molecular analyses were performed. The possible impact of the mutation was analyzed by online bioinformatics software. ClustalX-2.1-win and PyMol/Swiss-Pdb Viewer software were used for conservative analyses and to generate molecular graphic images, respectively.Results: The proband showed a lower limb venous thrombosis and acute pulmonary embolism infarction with reduced AT activity (50%). His mother, with subcutaneous ecchymosis, had reduced activities of AT and FII, of 44 and 5%, respectively. Molecular analysis showed that both the proband and his mother carried c.964A > T (p.Lys322stop) heterozygotes in SERPINC1. The difference was that his mother carried homozygous c.494C > T (p.Thr165Met) in F2, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein.Conclusion: This study identified a novel mutation of SERPINC1 and a missense mutation of F2, which may be the molecular mechanism leading to AT and FII deficiency in this family. It will help genetic diagnosis and counseling for thrombotic families.https://www.frontiersin.org/articles/10.3389/fgene.2022.832582/fullF2SERPINC1deep vein thrombosisacute pulmonary embolismsubcutaneous ecchymosisnovel mutation |
| spellingShingle | Haiyue Zhang Yiling Hu Dongli Pan Yuehua Xv Weifeng Shen Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes Frontiers in Genetics F2 SERPINC1 deep vein thrombosis acute pulmonary embolism subcutaneous ecchymosis novel mutation |
| title | Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes |
| title_full | Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes |
| title_fullStr | Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes |
| title_full_unstemmed | Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes |
| title_short | Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes |
| title_sort | genetic analysis of a pedigree with antithrombin and prothrombin compound mutations and antithrombin heterozygotes |
| topic | F2 SERPINC1 deep vein thrombosis acute pulmonary embolism subcutaneous ecchymosis novel mutation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.832582/full |
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