{"id":1264,"date":"2026-01-24T08:35:20","date_gmt":"2026-01-24T08:35:20","guid":{"rendered":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/monoallelic-mutations-in-duoxa2-are-associated-with-mild-permanent-hypothyroidism-and-goiter\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"monoallelic-mutations-in-duoxa2-are-associated-with-mild-permanent-hypothyroidism-and-goiter","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/monoallelic-mutations-in-duoxa2-are-associated-with-mild-permanent-hypothyroidism-and-goiter\/","title":{"rendered":"MONOALLELIC MUTATIONS IN DUOXA2 ARE ASSOCIATED WITH MILD PERMANENT HYPOTHYROIDISM AND GOITER"},"content":{"rendered":"<div class=\"article-authors\">\n<p>Ventura P.S.<sup>1<\/sup>, Azcona C.<sup>2<\/sup>, Clemente M.<sup>3<\/sup>, Albisu M.<sup>3<\/sup>, Audi L.<sup>3<\/sup>, Carrascosa A.<sup>3<\/sup> Visser T. J.<sup>1<\/sup>, Moreno J.C. <sup>1<\/sup><\/p>\n<\/div>\n<div class=\"article-institutes\"><sup>1<\/sup>Dept. Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, <sup>2<\/sup>Pediatrics, University Clinic of Navarra, Pamplona, Spain, <sup>3<\/sup>Pediatric Endocrinology, Vall d Hebron Hospital, Barcelona, Spain<\/div>\n<div class=\"article-abstract\">\n<h2>Abstract<\/h2>\n<p>Generation of H2O2 at the apical membrane of thyroid cells is essential for iodination of thyroglobulin. Dual oxidase 2 (DUOX2) is the catalytic core of the thyroidal H2O2 generator, and its deficiency leads to congenital hypothyroidism (CH) in humans and mice. The Dual oxidase maturation factor 2 (DUOXA2) is a recently identified endoplasmic reticulum (ER)-resident protein required for expression of DUOX2 activity.<br \/><strong>Aims:<\/strong> We aimed the identification of human DUOXA2 defects as a novel cause of dyshormonogenetic thyroid disease.<br \/>Patients and Methods: 83 CH patients with partial and total iodide organification defects were screened for mutations in the coding regions of DUOX2 and DUOXA2 genes.<br \/><strong>Results:<\/strong> Two missense mutations, W132L and G294E, were identified in DUOXA2. Mutations are heterozygous and are located in exons 4 and 6 of the gene, encoding a long intra-ER loop, predicted to interact with DUOX2, and the cytoplasmatic carboxy-terminal tail of the protein, respectively. Cotransfection of DUOX2 and DUOXA2 cDNAs in mammalian COS cells shows that W132L and G294E reduce in vitro H2O2 production capacity to 32% and 16% of wild type DUOXA2, respectively. W132L was identified in an European Caucasian girl diagnosed with non-goitrous CH, showing TSH of 25 mUI\/L at screening and 152 mUI\/L at serum confirmation with FreeT4 of 10,5 pmol\/L. Reevaluation at 3 years of age showed progressive increase of TSH and T4 treatment was re-introduced. G294E is present in an American-Hispanic girl not subjected to CH screening, consulting at 12 years of age for short stature. She was diagnosed with a large euthyroid goiter, with positive perchlorate test discharge of 24%, and T4 substitution was implemented. DUOX2 gene showed no pathogenic mutations in these patients.<br \/><strong>Conclusions:<\/strong> DUOXA2 monoallelic defects are associated with mild but permanent hypothyroidism and \/or goiter. DUOXA2 is a novel candidate gene for inheritable dyshormonogenetic thyroid defects.<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Ventura P.S.1, Azcona C.2, Clemente M.3, Albisu M.3, Audi L.3, Carrascosa A.3 Visser T. J.1, Moreno J.C. 1 1Dept. Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands, 2Pediatrics, University Clinic of Navarra, Pamplona, Spain, 3Pediatric Endocrinology, Vall d Hebron Hospital, Barcelona, Spain Abstract Generation of H2O2 at the apical membrane of thyroid cells is essential <a class=\"read-more\" href=\"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/monoallelic-mutations-in-duoxa2-are-associated-with-mild-permanent-hypothyroidism-and-goiter\/\">Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[45,2,9],"tags":[],"class_list":["post-1264","post","type-post","status-publish","format-standard","hentry","category-volume-7-issue-3","category-journal-articles","category-volume-7"],"_links":{"self":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1264","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/comments?post=1264"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1264\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1264"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1264"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1264"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}