AUTHOR=Kim Seondeuk , Lee Woo-Jin , Moon Jangsup , Jung Keun-Hwa 

TITLE=Utility of the SERPINC1 Gene Test in Ischemic Stroke Patients With Antithrombin Deficiency

JOURNAL=Frontiers in Neurology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.841934

DOI=10.3389/fneur.2022.841934

ISSN=1664-2295

ABSTRACT=<sec><title>Objective</title><p>Antithrombin (AT) plays a critical role in the coagulation system, and its deficiency induces hypercoagulability. AT deficiency is caused not only by inherited variants in the <italic>SERPINC1</italic> gene but also by acquired conditions. Therefore, AT deficiency alone could not ensure the presence of the <italic>SERPINC1</italic> mutation. We evaluated the utility of the <italic>SERPINC1</italic> gene test in ischemic stroke, an important clinical type of arterial thrombosis.</p></sec><sec><title>Methods</title><p>This retrospective, observational study investigated symptomatic patients who underwent the <italic>SERPINC1</italic> gene test because of decreased AT activity (&lt;80%) during 2009-2021 at a tertiary hospital. For the detection of sequence variants in the <italic>SERPINC1</italic> gene, direct Sanger sequencing and multiplex ligation-dependent probe amplification were performed. The phenotypes of patients with SERPINC1 gene mutations were examined, and the conditions associated with the pathogenic variants were analyzed.</p></sec><sec><title>Results</title><p>In our cohort (<italic>n</italic> = 19), 13 of 19 patients (68.4%) had the pathogenic variant of the <italic>SERPINC1</italic> gene. Ischemic stroke (<italic>n</italic> = 7) was significantly associated with the pathogenic variants (<italic>p</italic> = 0.044), and the pathogenicity detection rate was 100%. For any kind of arterial thrombosis (<italic>n</italic> = 8), the detection rate of the pathogenic variant was 87.5%, but was not statistically significant (<italic>p</italic> = 0.177). The detection rates of the pathogenic variant in ischemic stroke or arterial thrombosis groups were both higher than those in the venous thrombosis-only group (54.5%).</p></sec><sec><title>Conclusion</title><p>The <italic>SERPINC1</italic> gene test was useful in determining the cause of AT deficiency-related arterial thrombosis, especially ischemic stroke. We propose the diagnostic flow of <italic>SERPINC1</italic>-related ischemic stroke.</p></sec>