{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:45:00Z","timestamp":1772577900671,"version":"3.50.1"},"reference-count":20,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"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":[[2004]]},"abstract":"<jats:p>&lt;i&gt;Background:&lt;\/i&gt; Thyroid hormones are crucial for normal growth and central nervous system development. In recent years, germline variants of the TSH\u03b2 subunit gene have been identified as a cause of congenital TSH deficiency. &lt;i&gt;Methods:&lt;\/i&gt; We performed a genetic and clinical study in children from four European countries diagnosed with congenital isolated central hypothyroidism. &lt;i&gt;Results:&lt;\/i&gt; TSH\u03b2 gene analysis revealed compound heterozygosity for 145C\u2192T (Q49X) and 313delT (C105Vfs114X) in 1 infant and homozygous mutation 313delT (C105Vfs114X) in 5 patients. Although all presented with typical symptoms of hypothyroidism, diagnosis and treatment was delayed until 3\u20135 months in 5 of 6 patients. In a longitudinal sibpair analysis, thyroxine substitution initiated immediately after birth was effective to prevent developmental delay and growth retardation. &lt;i&gt;Conclusion:&lt;\/i&gt; Clinical awareness is required to detect hypothyroidism due to TSH\u03b2 mutations, which is not identified by TSH-based newborn screening. TSH\u03b2 variants C105Vfs114X and Q49X are the most frequent cause of this severe disorder in Europe, now for the first time observed in compound heterozygous state.<\/jats:p>","DOI":"10.1159\/000080071","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T09:38:42Z","timestamp":1092044322000},"page":"149-155","source":"Crossref","is-referenced-by-count":13,"title":["Compound Heterozygous and Homozygous Mutations of the TSH\u03b2 Gene as a Cause of Congenital Central Hypothyroidism in Europe"],"prefix":"10.1159","volume":"62","author":[{"given":"Beate","family":"Karges","sequence":"first","affiliation":[]},{"given":"Bruno","family":"LeHeup","sequence":"additional","affiliation":[]},{"given":"Eugen","family":"Schoenle","sequence":"additional","affiliation":[]},{"given":"Cintia","family":"Castro-Correia","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Fontoura","sequence":"additional","affiliation":[]},{"given":"Roland","family":"Pf\u00e4ffle","sequence":"additional","affiliation":[]},{"given":"Werner","family":"Andler","sequence":"additional","affiliation":[]},{"given":"Klaus-Michael","family":"Debatin","sequence":"additional","affiliation":[]},{"given":"Wolfram","family":"Karges","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2004,9,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1172%2FJCI118540"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.83.5.1762"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1203%2F00006450-199908000-00007"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.2002-020297"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1089%2Fthy.2000.10.387"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1203%2F01.PDR.0000034234.88317.B1"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.86.9.4468"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.87.1.336"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1089%2F105072502321085252"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.86.4.1600"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1089%2F105072503322238818"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1089%2Fthy.1999.9.523"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1056%2FNEJM197111042851902"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016%2FS0022-3476%2805%2981640-3"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016%2FS0022-3476%2886%2980276-1"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016%2F0014-5793%2895%2901384-9"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1210%2Fjc.82.5.1561"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1080%2F080352599750029330"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038%2F76041"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1210%2Fjcem-71-4-792"}],"container-title":["Hormone Research in Paediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/80071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/80071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T03:30:40Z","timestamp":1745465440000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000080071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004]]},"references-count":20,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2004,9,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000080071","archive":["Portico"],"relation":{},"ISSN":["1663-2818","1663-2826"],"issn-type":[{"value":"1663-2818","type":"print"},{"value":"1663-2826","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004]]}}}