{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T20:38:34Z","timestamp":1772656714770,"version":"3.50.1"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,4,15]],"date-time":"2007-04-15T00:00:00Z","timestamp":1176595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background\u2003<\/jats:bold> Iodide organification defects are frequently but not always associated with mutations in the thyroid peroxidase (<jats:italic>TPO<\/jats:italic>) gene and characterized by a positive perchlorate discharge test. These mutations phenotypically produce a congenital goitrous hypothyroidism, with an autosomal recessive mode of inheritance.<\/jats:p><jats:p><jats:bold>Objectives\u2003<\/jats:bold> In the present study we extended our initial molecular studies in six unrelated patients heterozygous for the <jats:italic>TPO<\/jats:italic> mutations, in order to identify the second mutation in this autosomal recessive disease.<\/jats:p><jats:p><jats:bold>Methods\u2003<\/jats:bold> The promoter and the complete coding regions of the human <jats:italic>TPO<\/jats:italic> and <jats:italic>DUOXA2<\/jats:italic> genes, along with the flanking regions of each intron were analysed by direct DNA sequencing.<\/jats:p><jats:p><jats:bold>Results\u2003<\/jats:bold> Four different inactivating <jats:italic>TPO<\/jats:italic> mutations were identified in two patients: two novel mutations (c.215delA [p.Q72fsX86] and c.1159G\u2192A [p.G387R]) and two previously reported (c.387delC [p.N129fsX208] and c.2422T\u2192C [p.C808R]), confirming the inheritance of two different compound heterozygous mutations, c.215delA\/c.2422T\u2192C and c.387delC\/c.1159G\u2192A. The remaining four patients did not show additional inactivating mutations in the <jats:italic>TPO<\/jats:italic> gene and all had only the wild type sequencing in the <jats:italic>DUOXA2<\/jats:italic> gene.<\/jats:p><jats:p><jats:bold>Conclusions\u2003<\/jats:bold> We have reported two patients with iodide organification defect caused by two compound heterozygous mutations, c.215delA\/c.2422T\u2192C [p.Q72fsX86\/p.C808R] and c.387delC\/c.1159G\u2192A [p.N129fsX208\/p.G387R], in the <jats:italic>TPO<\/jats:italic> gene and four patients with monoallelic <jats:italic>TPO<\/jats:italic> defect. Identification of the molecular basis of this disorder might be helpful for understanding the pathophysiology of congenital hypothyroidism.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2007.02869.x","type":"journal-article","created":{"date-parts":[[2007,6,4]],"date-time":"2007-06-04T09:56:14Z","timestamp":1180950974000},"page":"238-246","source":"Crossref","is-referenced-by-count":18,"title":["Two compound heterozygous mutations (c.215delA\/c.2422T\u2192C and c.387delC\/c.1159G\u2192A) in the thyroid peroxidase gene responsible for congenital goitre and iodide organification defect"],"prefix":"10.1111","volume":"67","author":[{"given":"Carina 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