{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T20:55:25Z","timestamp":1780606525535,"version":"3.54.1"},"reference-count":47,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2024]]},"abstract":"<b><i>Introduction:<\/i><\/b> Congenital hypothyroidism (CH), the most common neonatal endocrine disorder worldwide, can be caused by variants in the thyroid peroxidase (<i>TPO<\/i>) gene. This study aimed to identify <i>TPO<\/i> variants in Chinese patients with CH, analyze their impact on TPO function, and establish relationships between <i>TPO<\/i> genotypes and clinical characteristics. <b><i>Methods:<\/i><\/b> A total of 328 patients with CH were screened for <i>TPO<\/i> variants by performing whole-exome sequencing. The function of the detected <i>TPO<\/i> variants was investigated via transfection assays in vitro. The pathogenic effect of five novel variants was further assessed in silico. <b><i>Results:<\/i><\/b> Among 328 patients with CH, 19 <i>TPO<\/i> variants, including six novel ones, were identified in 43 patients. Eighteen patients (5.5%) carried biallelic <i>TPO<\/i> variants. In vitro experiments showed that TPO activity was impaired to varying degrees in 17 variants. Furthermore, we determined that a residual TPO enzyme activity threshold of 15% may serve as a criterion for differentiating CH severity. <b><i>Conclusions:<\/i><\/b> According to our study, the prevalence of <i>TPO<\/i> variants among Chinese patients with CH was 13.1%. Five novel variants led to impaired TPO function by altering its structure or by affecting its expression or cellular localization, which should result in impaired thyroid hormone synthesis. <\/jats:p>","DOI":"10.1159\/000533969","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:03:05Z","timestamp":1697058185000},"page":"353-364","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Screening and Functional Analysis of Thyroid Peroxidase Variants in Chinese Patients with Congenital 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