{"id":1265,"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\/genetic-characterization-of-iodide-organification-defects\/"},"modified":"2026-01-24T08:35:20","modified_gmt":"2026-01-24T08:35:20","slug":"genetic-characterization-of-iodide-organification-defects","status":"publish","type":"post","link":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/2026\/01\/24\/genetic-characterization-of-iodide-organification-defects\/","title":{"rendered":"GENETIC CHARACTERIZATION OF IODIDE ORGANIFICATION DEFECTS"},"content":{"rendered":"
Fugazzola L.1, Cortinovis F.2, Zamproni I.2, Vigone M. C.2, Muzza M.1, Cordella D.3, Beck-Peccoz P.1, Refetoff S.4, Weber G.2, Persani L.3 <\/div>\n
1<\/sup>Dept. of Medical Sciences, Endocrine Unit University of Milan, IRCCS Fondazione Policlinico, Milan, Italy, 2<\/sup>Department of Pediatrics, Lab of Pediatric Endocrinology University Vita-Salute S. Raffaele, Milan, Italy, 3<\/sup>Dept. of Medical Sciences University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy, 4<\/sup>Depts of Medicine and Pediatrics, University of Chicago, Illinois, USA<\/div>\n
\n

Abstract<\/h2>\n

Dyshormonogenesis accounts for about 30% of congenital hypothyroidism (CH) cases and the knowledge of underlying genetic defects is rapidly increasing. In the present study, 28 unrelated patients with CH and partial (PIOD) or total iodide organification defect (TIOD) were studied. Discharge after perchlorate test ranged 20-69% in PIOD and was >95% in TIOD probands. After informed consent, DUOX2, DUOXA2 and TPO genes were analyzed. In PIOD cases, 8 DUOX2 mutations were documented in 7\/21 patients. Mild permanent hypothyroidism was documented in 6, whereas 1 patient had transient CH. Five patients had heterozygous DUOX2 mutations, whereas 2 patients were compound heterozygotes for a nonsense and a missense mutation. Four of these mutations are novel (W414X, Y425X, Y475C and Q1023X), the missense Y475C being absent in 100 control alleles. No differences in iodide discharge was observed between patients carrying 1 or 2 DUOX2 mutations. In one Chinese PIOD patient with mild permanent hypothyroidism, a biallelic nonsense mutation was found in the DUOXA2 gene. Consistent with the DUOXA2 essential role in the maturation and translocation to the plasma membrane of DUOX2, studies of mutant DUOXA2 documented an almost complete loss of DUOX2 activity. No TPO mutations were detected in the remaining 13 PIOD patients. At variance, all patients with TIOD had mutations in the TPO gene. In particular, 4\/6 patients were homozygote or compound heterozygotes, while 2 patients were heterozygous for a single mutation. These latter cases presented with the association of sensorineural hearing loss, but the possible involvement of PDS mutations was excluded. In TIOD cases the degree of hypothyroidism was always severe. In conclusion, PIOD with mild permanent\/transient CH was associated in about 40% of cases with defects in the H2O2 generator system (DUOX2, DUOXA2). On the other hand, TPO defects were invariably associated with TIOD and severe CH. <\/div>\n","protected":false},"excerpt":{"rendered":"

Fugazzola L.1, Cortinovis F.2, Zamproni I.2, Vigone M. C.2, Muzza M.1, Cordella D.3, Beck-Peccoz P.1, Refetoff S.4, Weber G.2, Persani L.3 1Dept. of Medical Sciences, Endocrine Unit University of Milan, IRCCS Fondazione Policlinico, Milan, Italy, 2Department of Pediatrics, Lab of Pediatric Endocrinology University Vita-Salute S. Raffaele, Milan, Italy, 3Dept. of Medical Sciences University of Milan, 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-1265","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\/1265","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=1265"}],"version-history":[{"count":0,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/posts\/1265\/revisions"}],"wp:attachment":[{"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/media?parent=1265"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/categories?post=1265"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/peaceful-mccarthy.213-158-90-25.plesk.page\/index.php\/wp-json\/wp\/v2\/tags?post=1265"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}