{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:45:44Z","timestamp":1771303544828,"version":"3.50.1"},"reference-count":34,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Res Paediatr"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Central hypothyroidism (CH) in children is rare and may be due to a variety of genetic defects. Most of these defects, but not all, are associated with additional pituitary hormone deficits. In a young child presenting with CH, it is important to determine whether additional pituitary hormone deficiencies are present, but this may be difficult to establish clinically. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; We describe the clinical characteristics of two young siblings, aged 6 months and 2 years, presenting with isolated CH. Whole exome sequencing was performed to determine the genetic basis of isolated CH. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; A homozygous frameshift mutation of &lt;i&gt;PROP1&lt;\/i&gt; (296delGA) was identified in both probands. Defects in &lt;i&gt;PROP1&lt;\/i&gt; cause progressive deficiency of multiple pituitary hormones. Based on this genetic diagnosis, further clinical testing was performed that demonstrated growth hormone deficiency in one sibling. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; PROP1 deficiency may present as isolated CH at a very young age. In disorders with multiple potential causative genes, whole exome sequencing may facilitate rapid genetic diagnosis and lead to important changes in clinical management.<\/jats:p>","DOI":"10.1159\/000350013","type":"journal-article","created":{"date-parts":[[2013,5,6]],"date-time":"2013-05-06T10:12:33Z","timestamp":1367835153000},"page":"379-386","source":"Crossref","is-referenced-by-count":12,"title":["Isolated Central Hypothyroidism in Young Siblings as a Manifestation of PROP1 Deficiency: Clinical Impact of Whole Exome Sequencing"],"prefix":"10.1159","volume":"79","author":[{"given":"Ari J.","family":"Wassner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie E.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana","family":"Hechter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Dauber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2013,5,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(79)80133-X"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80276-1"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-1616"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-2162"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-2444"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(86)80112-3"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1968.02100010275018"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/nature09534"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0008"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2453"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.4.1600"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.5.1561"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc0808557"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.5.1645"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.9.4529"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2005.02291.x"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0150"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1159\/000308169"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-010-0278-8"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03326.x"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-147"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.12.4556"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1210\/jc.85.1.390"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0661"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1500257"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.2002.01550.x"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.82.8.2423"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2173"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-011-0614-7"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2938"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-1334"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/350013","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/350013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T18:14:03Z","timestamp":1745432043000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000350013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,7,1]]},"published-print":{"date-parts":[[2013,7,16]]}},"URL":"https:\/\/doi.org\/10.1159\/000350013","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}