{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:50:43Z","timestamp":1786978243433,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,2,7]],"date-time":"2021-02-07T00:00:00Z","timestamp":1612656000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Sub\u2010heading<\/jats:title>\n                    <jats:p>Compound hemizygous variants in SERPINA7 gene.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Thyroxine\u2010binding globulin (TBG) is encoded by\n                      <jats:italic>SERPINA7<\/jats:italic>\n                      (OMIM. 314200) which is located on Xq22.3.\n                      <jats:italic>SERPINA7<\/jats:italic>\n                      variants caused TBG deficiency which does not require treatment, but the decreased thyroxine may be misdiagnosed as hypothyroidism. We discovered some variants of TBG caused by alterations that differ from previously reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we enrolled 32 subjects from 10 families and sequenced the\n                      <jats:italic>SERPINA7<\/jats:italic>\n                      genes of TBG\u2010deficient subjects. Then, variants were analyzed to assess their effect on TBG expression and secretion. Bioinformatics database, protein structure, and dynamics simulation were used to evaluate the deleterious effects. Finally, we identified 2 novel and 4 known variants, and found 26 of 30 subjects carried the p.L303F. The DynaMut predictions indicated the variants (p.E91K, p.I92T, p.R294C, and p.L303F) exhibited decreased stability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Analyses revealed the p.L303F change the protein stability and flexibility, and it had an impact on the function of TBG, but when coexisted with other variants it might change the conformational structure of the protein and aggravate the damage to the protein. We speculated that the existence of a higher number of variants resulted in lower TBG secretion.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.1571","type":"journal-article","created":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T18:00:43Z","timestamp":1612807243000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Compound hemizygous variants in\n                    <i>SERPINA7<\/i>\n                    gene cause thyroxine\u2010binding globulin deficiency"],"prefix":"10.1002","volume":"9","author":[{"given":"Yanlan","family":"Fang","sequence":"first","affiliation":[{"name":"Pediatric Department The 1st Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatric Department The 1st Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Pediatric Department The 1st Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Pediatric Department The 1st Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-7406","authenticated-orcid":false,"given":"Li","family":"Liang","sequence":"additional","affiliation":[{"name":"Pediatric Department The 1st Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2015.09.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.20.7708"},{"key":"e_1_2_9_4_1","first-page":"368","article-title":"Identification of thyroxine\u2010binding globulin\u2010San Diego in a family from Houston and its characterization by in vitro expression using Xenopus oocytes","volume":"85","author":"Janssen O. 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