{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:23:43Z","timestamp":1777940623896,"version":"3.51.4"},"reference-count":26,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Thyroid dysfunction is common in newborn infants with Down's syndrome (DS), but defects causing classic thyroid dysgenesis (TD) with permanent congenital hypothyroidism (CH) have not been described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>\n                      We studied a girl with DS and CH who had a mutation in the promoter sequence of the\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A female infant was found to have trisomy 21 and CH, with a venous thyrotropin (TSH) of &gt;150\u2009mU\/L and a free thyroxine (fT4) of 15.1 pmol\/L (day 12). Thyroid peroxidase antibodies and thyroglobulin antibodies were elevated. Scintigraphy showed normal uptake, but ultrasound identified a small gland with heterogenous echotexture and cystic changes. Sequence analysis of the\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      gene revealed a new heterozygous maternally inherited mutation (\u22123C&gt;T) close to the transcription initiation site. Electromobility shift assay studies of the wild type and the mutant\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      sequence incubated with nuclear extracts from PCCL3 cells exhibited that the sequence at position \u22123 is not involved in specific protein binding. However, the mutant\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      promoter showed a significantly reduced transcriptional activation of a\n                      <jats:italic toggle=\"yes\">luciferase<\/jats:italic>\n                      reporter gene\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      tested in HEK, PCCL3, as well as in HeLa cells, indicating that this mutation is very likely to lead to reduced\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The persistent CH in this patient with DS is likely to be attributable to the diminished\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      expression due to a new heterozygous mutation in the\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      promoter sequence. Our case shows that true CH may occur in DS, as in the general population. Furthermore, it is possible that the trisomy 21 itself may have resulted in a more severe phenotypic expression of the\n                      <jats:italic toggle=\"yes\">PAX8<\/jats:italic>\n                      mutation in the child than the mother.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0248","type":"journal-article","created":{"date-parts":[[2014,2,5]],"date-time":"2014-02-05T12:21:26Z","timestamp":1391602886000},"page":"939-944","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["A New Mutation in the Promoter Region of the\n                    <i>PAX8<\/i>\n                    Gene Causes True Congenital Hypothyroidism with Thyroid Hypoplasia in a Girl with Down's Syndrome"],"prefix":"10.1177","volume":"24","author":[{"given":"Pia","family":"Hermanns","sequence":"first","affiliation":[{"name":"Johannes Gutenberg University Medical School","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott","family":"Shepherd","sequence":"additional","affiliation":[{"name":"Royal Hospital for Sick Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Mansor","sequence":"additional","affiliation":[{"name":"Forth Valley Royal Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Schulga","sequence":"additional","affiliation":[{"name":"Forth Valley Royal Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jez","family":"Jones","sequence":"additional","affiliation":[{"name":"Royal Hospital for Sick Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Royal Hospital for Sick Children"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Pohlenz","sequence":"additional","affiliation":[{"name":"Johannes Gutenberg University Medical School","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,6,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0028"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0116"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-374430-2.00009-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0398"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2005-1238"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2341"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b3794"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2013.26"},{"key":"e_1_3_3_10_2","first-page":"57","article-title":"Thyroid function in patients with Down syndrome: preliminary results from non-institutionalized patients in the Veneto region","volume":"7","author":"Pozzan GB","year":"1990","unstructured":"Pozzan GB, , Rigon F, , Girelli ME, , Rubello D, , Busnardo B, , Baccichetti C. 1990. Thyroid function in patients with Down syndrome: preliminary results from non-institutionalized patients in the Veneto region. Am J Med Genet Suppl, 7:57\u201358.","journal-title":"Am J Med Genet Suppl"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021303"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.15.6419"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.9.4350"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(84)80544-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(98)70369-5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1159\/000341149"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2006.16.671"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2011-300806"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1190"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.20.8125"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.72.121801.161520"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.6251548"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-306"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-12-0410"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2012.0649"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-83"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.86.8.7765"}],"container-title":["Thyroid\u00ae"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/thy.2013.0248","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0248","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/thy.2013.0248","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T05:55:40Z","timestamp":1777701340000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/thy.2013.0248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,6]]}},"alternative-id":["10.1089\/thy.2013.0248"],"URL":"https:\/\/doi.org\/10.1089\/thy.2013.0248","relation":{},"ISSN":["1050-7256","1557-9077"],"issn-type":[{"value":"1050-7256","type":"print"},{"value":"1557-9077","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,6]]}}}