{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T16:05:21Z","timestamp":1762272321002,"version":"3.40.4"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470044","81500689","81502063","81170812"],"award-info":[{"award-number":["81470044","81500689","81502063","81170812"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Thyroid dysgenesis (TD) accounts for most cases of congenital hypothyroidism. Although mutations in thyroid hormone receptor \u03b2 (<jats:italic>THRB<\/jats:italic>) have been identified in TD, the mutational spectrum of <jats:italic>THRB<\/jats:italic> and phenotype\u2010genotype correlations have not been fully elucidated. In this study, we aimed to find mutations of <jats:italic>THRB<\/jats:italic>, examine the functions of these mutations, and attempt to elucidate the relationship between <jats:italic>THRB<\/jats:italic> and TD. Thus, we screened the exons of <jats:italic>THRB<\/jats:italic> in 280 patients with TD and 200 normal subjects in samples collected from China. We performed cell morphology assays, MTT assays, flow cytometric analyses, and a quantitative reverse\u2010transcription polymerase chain reaction in human thyroid follicular epithelial cells (Nthy\u2010ori cell line) to examine the impact of <jats:italic>THRB<\/jats:italic> mutations. In two unrelated patients, two novel missense mutations, c.76G&gt;A (p.D26N) and c.107G&gt;A (p.C36Y), were identified in <jats:italic>THRB<\/jats:italic>. Functional studies suggested that the C36Y mutant caused changes in morphology, inhibiting cell proliferation and promoting apoptosis in a human thyroid cell line. In addition, we found that messenger RNA expressions of thyroglobulin (<jats:italic>TG<\/jats:italic>) and the Na<jats:sup>+<\/jats:sup>\/I<jats:sup>\u2212<\/jats:sup> symporter (<jats:italic>NIS<\/jats:italic>) were decreased in a time\u2010dependent manner in mutant <jats:italic>THRB<\/jats:italic> compared with the wild type. To our knowledge, this is the first study to document the prevalence of <jats:italic>THRB<\/jats:italic> mutations and the genotype\u2010phenotype spectrum of TD in a Chinese population. We characterized the function of a C36Y mutation, which reduced cell proliferation and increased cell death in thyroid epithelial cells. This study provides further evidence for genetic <jats:italic>THRB<\/jats:italic> defects and disease mechanisms in TD.<\/jats:p>","DOI":"10.1002\/jcb.27264","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T05:17:50Z","timestamp":1533619070000},"page":"9474-9482","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel <i>THRB<\/i> mutation analysis in congenital hypothyroidism with thyroid dysgenesis"],"prefix":"10.1002","volume":"119","author":[{"given":"Zhixia","family":"Zhou","sequence":"first","affiliation":[{"name":"Center for Tumor Molecular Biology, Institute for Translational Medicine, Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1505-754X","authenticated-orcid":false,"given":"Chengyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Qingdao Women and Children\u2019s Hospital Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenmiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Prenatal Diagnosis Center Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengli","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Qingdao University Qingdao China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Medical School of Qingdao University Qingdao 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