{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:23:33Z","timestamp":1789943013170,"version":"4.0.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"5","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":["eur j endocrinol"],"published-print":{"date-parts":[[2007,5]]},"abstract":"\n Objective<\/jats:italic>\n : Mutations in\n NKX2.1<\/jats:italic>\n ,\n NKX2.5<\/jats:italic>\n ,\n FOXE1<\/jats:italic>\n and\n PAX8<\/jats:italic>\n genes, encoding for transcription factors involved in the development of the thyroid gland, have been identified in a minority of patients with syndromic and non-syndromic congenital hypothyroidism (CH).\n <\/jats:p>\n \n Design<\/jats:italic>\n : In a phenotype-selected cohort of 170 Czech paediatric and adolescent patients with non-goitre CH, including thyroid dysgenesis, or non-goitre early-onset hypothyroidism,\n PAX8<\/jats:italic>\n ,\n NKX2.1<\/jats:italic>\n ,\n NKX2.5<\/jats:italic>\n ,\n FOXE1<\/jats:italic>\n and\n HHEX<\/jats:italic>\n genes were analysed for mutations.\n <\/jats:p>\n \n Methods: NKX2.1<\/jats:italic>\n ,\n NKX2.5<\/jats:italic>\n ,\n FOXE1<\/jats:italic>\n and\n HHEX<\/jats:italic>\n genes were directly sequenced in patients with syndromic CH.\n PAX8<\/jats:italic>\n mutational screening was performed in all 170 patients by single-stranded conformation polymorphism, followed by direct sequencing of samples with abnormal findings. The R52P PAX8 mutation was functionally characterized by DNA binding studies.\n <\/jats:p>\n \n Results<\/jats:italic>\n : We identified a novel PAX8 mutation R52P, dominantly inherited in a three-generation pedigree and leading to non-congenital, early-onset, non-goitre, non-autoimmune hypothyroidism with gradual postnatal regression of the thyroid size and function. The R52P PAX8 mutation results in the substitution of a highly conserved residue of the DNA-binding domain with a loss-of-function effect.\n Conclusions<\/jats:italic>\n : The very low frequency of genetic defects in a population-based cohort of children affected by non-goitre congenital and early-onset hypothyroidism, even in a phenotype-focussed screening study, suggests the pathogenetic role of either non-classic genetic mechanisms or the involvement of genes unknown so far. Identification of a novel\n PAX8<\/jats:italic>\n mutation in a particular variant of non-congenital early-onset hypothyroidism indicates a key function of PAX8 in the postnatal growth and functional maintenance of the thyroid gland.\n <\/jats:p>","DOI":"10.1530\/eje-06-0709","type":"journal-article","created":{"date-parts":[[2007,4,27]],"date-time":"2007-04-27T10:18:20Z","timestamp":1177669100000},"page":"521-529","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":77,"title":["Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism"],"prefix":"10.1093","volume":"156","author":[{"given":"Eva","family":"Al Taji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heike","family":"Biebermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zden\u030cka","family":"Li\u0301manova\u0301","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Hni\u0301kova\u0301","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Zikmund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof","family":"Dame","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Gru\u0308ters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Lebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Krude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/156\/5\/1560521.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/156\/5\/1560521.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T11:19:51Z","timestamp":1676373591000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/156\/5\/521\/6695860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5]]},"references-count":0,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/eje-06-0709","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1089392.543642","asserted-by":"object"}]},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5]]}}}