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However, no reliable genotype\u2013phenotype relationship has been found in patients with\n                    <jats:italic>DUOX2<\/jats:italic>\n                    mutations. In this study,\n                    <jats:italic>DUOX2<\/jats:italic>\n                    mutations were screened in 266 CH patients, and the enzymatic activity of 89\n                    <jats:italic>DUOX2<\/jats:italic>\n                    variants was determined in vitro. Furthermore, the\n                    <jats:italic>DUOX2<\/jats:italic>\n                    residual activity in 76 CH patients caused by\n                    <jats:italic>DUOX2<\/jats:italic>\n                    biallelic mutations was calculated. The thyroid\u2010stimulating hormone (TSH) and free thyroxine (FT4) levels were found to be higher and lower in patients with\n                    <jats:italic>DUOX2<\/jats:italic>\n                    residual activity \u226422%, respectively, compared to patients with residual enzymatic activity &gt;22%. Moreover, we interpreted the pathogenicity of\n                    <jats:italic>DUOX2<\/jats:italic>\n                    variants by applying the ACMG classification criteria with or without PS3\/BS3 evidence. The results indicated that residual\n                    <jats:italic>DUOX2<\/jats:italic>\n                    enzymatic activity was closely related to the clinical phenotypes of CH patients caused by\n                    <jats:italic>DUOX2<\/jats:italic>\n                    biallelic mutations. These findings suggest that the residual enzymatic activity of 22% may be a cutoff value for estimating the severity of hypothyroidism in CH patients with biallelic\n                    <jats:italic>DUOX2<\/jats:italic>\n                    mutations. Well\u2010established functional studies are useful and necessary to evaluate the pathogenicity of\n                    <jats:italic>DUOX2<\/jats:italic>\n                    variants, improving the accuracy and scope of genetic consultations.\n                  <\/jats:p>","DOI":"10.1111\/cge.14065","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T05:10:08Z","timestamp":1632633008000},"page":"713-721","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Correlation of\n                    <scp>DUOX2<\/scp>\n                    residual enzymatic activity with phenotype in congenital hypothyroidism caused by biallelic\n                    <scp>\n                      <i>DUOX2<\/i>\n                    <\/scp>\n                    defects"],"prefix":"10.1111","volume":"100","author":[{"given":"Feng","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics &amp; Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, State Key Laboratory of Medical Genomics Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui\u2010Jia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics &amp; Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People\u2019s Hospital Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Endocrinology, Shanghai Ninth People\u2019s Hospital, State Key Laboratory of Medical Genomics Shanghai Jiao Tong University School of Medicine  Shanghai 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