AUTHOR=Zhang Haiyue , Hu Yiling , Pan Dongli , Xv Yuehua , Shen Weifeng 

TITLE=Genetic Analysis of a Pedigree With Antithrombin and Prothrombin Compound Mutations and Antithrombin Heterozygotes

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.832582

DOI=10.3389/fgene.2022.832582

ISSN=1664-8021

ABSTRACT=<p><bold>Background and Aims:</bold> Antithrombin (AT) is the most important physiological inhibitor <italic>in vivo</italic>, 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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 &gt; T (p.Lys322stop) heterozygotes in <italic>SERPINC1</italic>. The difference was that his mother carried homozygous c.494C &gt; T (p.Thr165Met) in <italic>F2</italic>, while the proband was wild type. Bioinformatics and model analysis indicated that mutations may destroy the function and structure of AT and FII protein.</p><p><bold>Conclusion:</bold> This study identified a novel mutation of <italic>SERPINC1</italic> and a missense mutation of <italic>F2</italic>, 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.</p>