{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T19:25:15Z","timestamp":1784748315097,"version":"3.55.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Thyroid peroxidase (TPO) is essential for thyroid hormone biosynthesis. <jats:italic>TPO<\/jats:italic> mutations might lead to congenital hypothyroidism. In the present study, we analysed the function of a compound heterozygous <jats:italic>TPO<\/jats:italic> mutation in a Chinese family.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>We studied a 23\u2010year\u2010old Chinese girl with a history of growth retardation and severe constipation from the age of 3\u00a0months, who was diagnosed as having congenital hypothyroidism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA was extracted from peripheral blood samples obtained from the patient's family members. The genomic DNA was sequenced to detect mutations in a panel of genes associated with congenital hypothyroidism. Bioinformatic analysis and structural modelling predicted the potential disease\u2010causing potential mutant genes and the microstructure of the mutant protein, respectively. Western blotting and ELISA were used to measure protein expression, and guaiacol oxidation assay measured the TPO activity of the mutant protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a compound heterozygous mutation (c.C1993T, c.T2473C) in the <jats:italic>TPO<\/jats:italic> gene. Bioinformatic analysis predicted that the <jats:italic>TPO<\/jats:italic> mutations were potentially disease causing. Structural modelling predicted damage to the microstructure of the mutant TPO protein. Western blotting and ELISA showed reduced protein levels of the mutant TPO protein compared with that of the wild\u2010type protein. The mutant TPO protein showed weaker activity compared with that of the wild\u2010type protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A novel compound heterozygous mutation of <jats:italic>TPO<\/jats:italic> gene was identified in a Chinese family. This mutation might alter the extracellular microstructure of TPO, and decrease its expression and the activity, resulting in congenital hypothyroidism.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14253","type":"journal-article","created":{"date-parts":[[2020,5,19]],"date-time":"2020-05-19T06:15:01Z","timestamp":1589868901000},"page":"499-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Functional analysis of thyroid peroxidase gene mutations resulting in congenital hypothyroidism"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4056-8592","authenticated-orcid":false,"given":"Defa","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, Institute of Endocrine, Liaoning Provincial Key Laboratory of Endocrine Diseases The First Hospital of China Medical University Shenyang 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