{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:58:30Z","timestamp":1791845910176,"version":"4.3.4"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T00:00:00Z","timestamp":1613952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To elucidate the molecular cause in a well-characterized cohort of patients with Congenital Hypothyroidism (CH) and Dyshormonogenesis (DH) by using targeted next-generation sequencing (TNGS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Study design<\/jats:title><jats:p>We studied 19 well-characterized patients diagnosed with CH and DH by targeted NGS including genes involved in thyroid hormone production. The pathogenicity of novel mutations was assessed based on <jats:italic>in silico<\/jats:italic> prediction tool results, functional studies when possible, variant location in important protein domains, and a review of the recent literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TNGS with variant prioritization and detailed assessment identified likely disease-causing mutations in 10 patients (53%). Monogenic defects most often involved <jats:italic>TG<\/jats:italic>, followed by <jats:italic>DUOXA2<\/jats:italic>, <jats:italic>DUOX2<\/jats:italic>, and <jats:italic>NIS<\/jats:italic> and were usually homozygous or compound heterozygous. Our review shows the importance of the detailed phenotypic description of patients and accurate analysis of variants to provide a molecular diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In a clinically well-characterized cohort, TNGS had a diagnostic yield of 53%, in accordance with previous studies using a similar strategy. <jats:italic>TG<\/jats:italic> mutations were the most common genetic defect. TNGS identified gene mutations causing DH, thereby providing a rapid and cost-effective genetic diagnosis in patients with CH due to DH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2020.545339","type":"journal-article","created":{"date-parts":[[2021,2,22]],"date-time":"2021-02-22T05:48:17Z","timestamp":1613972897000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["High Diagnostic Yield of Targeted Next-Generation Sequencing in a Cohort of Patients With Congenital Hypothyroidism Due to Dyshormonogenesis"],"prefix":"10.3389","volume":"11","author":[{"given":"Athanasia","family":"Stoupa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Al Hage Chehade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Chaabane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulanjalee","family":"Kariyawasam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Szinnai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Hanein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bole-Feysot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Fourrage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Nitschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Thalassinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mouna","family":"Mnif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Baron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"De Kerdanet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Reynaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Barat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mongia","family":"Hachicha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neila","family":"Belguith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Polak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Carr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annepidem.2015.11.005","article-title":"Increased incidence of congenital hypothyroidism in France from 1982 to 2012: a nationwide multicenter analysis","volume":"26","author":"Barry","year":"2016","journal-title":"Ann Epidemiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1073","article-title":"Is the incidence of congenital hypothyroidism really increasing? 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