{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:51:29Z","timestamp":1777002689781,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      AT and PC are key components of the anticoagulant system. Mutations in their encoding genes,\n                      <jats:italic>SERPINC1<\/jats:italic>\n                      and\n                      <jats:italic>PROC<\/jats:italic>\n                      , can lead to insufficient protein levels or impaired function, thereby increasing an individual's susceptibility to venous thromboembolism (VTE). In this study, we describe the clinical characteristics and functional effects of compound heterozygous mutations in\n                      <jats:italic>SERPINC1<\/jats:italic>\n                      and\n                      <jats:italic>PROC<\/jats:italic>\n                      in two pedigrees.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Anticoagulant protein activity and antigen levels were evaluated in family members. Targeted sequencing was performed using next\u2010generation sequencing (NGS) and CNVplex technology. The identified variants were assessed for evolutionary conservation, pathogenic potential, and their impact on protein structure. Thrombin generation was measured using the calibrated automated thrombogram (CAT) assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The PC:A and PC:Ag of proband 1 were decreased to 57% and 59.2%, and PC:A of proband 2 was decreased to 68%. The\n                      <jats:italic>SERPINC1<\/jats:italic>\n                      (OMIM#:613118) and PROC (OMIM#:176860) gene analysis indicated that there were c.400+5G&gt;A and c.883G&gt;A in proband 1, c.811C&gt;T and c.880C&gt;T in proband 2, respectively. These mutation sites are highly conserved across homologous species. Bioinformatics analysis predicts their potential pathogenicity, suggesting that they may alter the three\u2010dimensional structures of both AT and PC proteins, thereby compromising their functional integrity. Thrombin generation assays revealed that two AT mutation carriers exhibited varying degrees of elevated ETP. In the presence of sTM, two PC mutation carriers showed significantly impaired plasma anticoagulant function without a significant reduction in thrombin generation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In both pedigrees, we identified two distinct mutations in AT and PC. Dual mutations in\n                      <jats:italic>SERPINC1<\/jats:italic>\n                      and\n                      <jats:italic>PROC<\/jats:italic>\n                      confer markedly increased VTE susceptibility.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70191","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:21:30Z","timestamp":1774585290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of the Phenotype and Gene Mutations of Two Families With Combined Mutations of Anticoagulant Protein Genes"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6208-4763","authenticated-orcid":false,"given":"Yueli","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjieying","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanzhong","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Wenzhou TCM Hospital of Zhejiang Chinese Medical University  Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2016.04.011"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-0761"},{"issue":"3","key":"e_1_2_11_4_1","article-title":"Thrombophilia TeXi Wu,Ous Thrombosis","volume":"377","author":"Connors J. 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