{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:49Z","timestamp":1753869409497,"version":"3.41.2"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Inherited AT deficiency is an autosomal\u2010dominant thrombophilic disorder usually caused by various <jats:italic>SERPINC1<\/jats:italic> defects associated with a high risk of recurrent venous thromboembolism. In this article, the phenotype, gene mutation, and molecular pathogenic mechanisms were determined in three pedigrees with inherited AT deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Coagulation indices were examined on STAGO STA\u2010R\u2010MAX analyzer. The AT:Ag was analyzed by ELISA. All exons and flanking sequences of <jats:italic>SERPINC1<\/jats:italic> were amplified by PCR. AT wild type and three mutant expression plasmids were constructed and then transfected into HEK293FT cells. The expression level of AT protein was analyzed by ELISA and Western blot.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The AT:A and AT:Ag of probands 1 and 3 were decreased to 49% and 52\u2009mg\/dL, 38% and 44\u2009mg\/dL, respectively. The AT:A of proband 2 was decreased to 32%. The <jats:italic>SERPINC1<\/jats:italic> gene analysis indicated that there was a p.Ile421Thr in proband 1, a p.Leu417Gln in proband 2, and a p.Met252Thr in proband 3, respectively. The AT mRNA expression level of the three mutants was not significantly different from AT\u2010WT by qRT\u2010PCR. The results of ELISA and Western blot tests showed that the AT\u2010M252T and AT\u2010I421T mutants had a higher AT expression than the AT wild type (AT\u2010WT), and the AT protein expression of AT\u2010L417Q mutants had no significant difference compared with AT\u2010WT in the cell lysate. The AT expression levels of AT\u2010M252T and AT\u2010I421T mutants were lower than that of AT\u2010WT, and there was no significant difference between AT\u2010L417Q mutant and AT\u2010WT in the supernatant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The p.I421T and p.M252T mutations affected the secretion of AT protein leading to type I AT deficiency of probands 1 and 3. The p.Leu417Gln mutation was responsible for the impaired or ineffective activity AT protein in proband 2 and caused type II AT deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24732","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T11:50:18Z","timestamp":1666353018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analysis of phenotype and gene mutation in three pedigrees with inherited antithrombin deficiency"],"prefix":"10.1002","volume":"36","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[{"name":"School of Laboratory Medicine and Life Science Wenzhou Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory The First Affiliated Hospital of Wenzhou Medical University  Wenzhou 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