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It is an attractive candidate gene for congenital hypothyroidism (CH). This study aimed to identify DUOXA2 variants in Chinese CH patients, analyze the function of the variants, and explore the genotype\u2013phenotype relationship.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A total of 599 patients with CH were recruited for screening DUOXA2 variants by performing targeted next-generation sequencing or whole exome sequencing. Detailed clinical data were collected for statistical analysis. The biological function of the identified DUOXA2 variants was detected in vitro.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 13 variants including 6 novel variants were detected in the DUOXA2 gene, showing a 6.7% rate in variant carrying (40\/599). Ten variants disrupted the enzyme activity of DUOX2, resulting in impaired H2O2 production. In addition, we found that oligogenic mutation patterns within the DUOX system were prevalent among Chinese patients with CH. The cases in the DUOXA2-mutated group were milder and more likely to manifest as normal thyroid size than those in the nonmutated group.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study greatly expanded the variant spectrum of the DUOXA2 gene. Pedigree and in vitro functional studies improved the accuracy of genetic counseling. The genotype\u2013phenotype relationship of DUOXA2 broadened the understanding of the CH phenotype spectrum.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvaf123","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:00:47Z","timestamp":1749805247000},"page":"21-30","source":"Crossref","is-referenced-by-count":6,"title":["Large-scale screening and functional study of <i>DUOXA2<\/i> variant in 599 Chinese patients with congenital hypothyroidism"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9853-168X","authenticated-orcid":false,"given":"Hai-Yang","family":"Zhang","sequence":"first","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine , No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011 ,","place":["China"]},{"name":"Department of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cao-Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Affiliated Hospital of Nantong University , Nantong 226000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Yao","family":"Wu","sequence":"additional","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine , No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine , No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Fujian Provincial Hospital , Fuzhou 350001 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine , No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine , No. 639, Zhizaoju Road, Huangpu District, Shanghai 200011 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9609-5803","authenticated-orcid":false,"given":"Huai-Dong","family":"Song","sequence":"additional","affiliation":[{"name":"The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, State Key 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