{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:27:15Z","timestamp":1791404835621,"version":"4.3.3"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,7]],"date-time":"2013-01-07T00:00:00Z","timestamp":1357516800000},"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":[[2013,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Monocarboxylate transporter 8 (<jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8) is an essential thyroid hormone (<jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content>) transporter as humans with <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations have severe neurological and endocrine abnormalities. The objectives are (i) to identify novel <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations and (ii) to assess their functional relevance; (iii) to describe the effects of block\u2010and\u2010replace treatment in an MCT8 patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">TOP\u2010R<\/jats:styled-content> study is a cross\u2010sectional nation\u2010wide multicentre study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>Subjects with unexplained mental retardation (<jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>) were screened for <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified three mutations: p.F501del (previously described), p.L492P and p.T162T. The F501del and L492P mutants, but not the T162T mutant, showed diminished T3, T4 and <jats:styled-content style=\"fixed-case\">rT<\/jats:styled-content>3 transport in transfected cells. TH transport in T162T fibroblasts was also not affected. One patient was treated with block\u2010and\u2010replace therapy to normalize serum <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> levels. The results indicated a slow onset of the decrease in serum T4 and T3 by successive treatment with methimazole and <jats:styled-content style=\"fixed-case\">PTU<\/jats:styled-content>, and eventually their complete normalization by administration of <jats:styled-content style=\"fixed-case\">LT<\/jats:styled-content>4 with <jats:styled-content style=\"fixed-case\">PTU<\/jats:styled-content> but not with methimazole. The frequency of <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations in males with <jats:styled-content style=\"fixed-case\">X<\/jats:styled-content>\u2010linked <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> approximately 3\u00b79%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified several <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations in a cohort of subjects with unexplained <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>. We demonstrated the pathogenicity of two missense mutations. The synonymous variant did not affect <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> transport. Block\u2010and\u2010replace therapy of one patient reversed the <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> abnormalities. Our data suggest a decreased <jats:styled-content style=\"fixed-case\">TH<\/jats:styled-content> secretion rate and an increased T4 to T3 conversion by the type I deiodinase in patients with <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations. Our study indicates that <jats:styled-content style=\"fixed-case\">MCT<\/jats:styled-content>8 mutations are a relatively frequent cause of X\u2010linked <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.12023","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T05:59:09Z","timestamp":1346133549000},"page":"310-315","source":"Crossref","is-referenced-by-count":64,"title":["Identification, functional analysis, prevalence and treatment of monocarboxylate transporter 8 (<i><scp>MCT<\/scp>8<\/i>) mutations in a cohort of adult patients with mental retardation"],"prefix":"10.1111","volume":"78","author":[{"given":"W. Edward","family":"Visser","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Vrijmoeth","sequence":"additional","affiliation":[{"name":"General Practitioner Baalderborg Hardenberg The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank E.","family":"Visser","sequence":"additional","affiliation":[{"name":"\u2018s Heeren Loo Ermelo The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem Frans M.","family":"Arts","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Sophia's Children Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"van Toor","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo J.","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,1,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17226-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/380999"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/431313"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20808"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2007.11.003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2011.04089.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2570"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0256"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0262"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2719"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-007-0589-6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.367"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.66"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg055"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135308"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42113"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0593"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0900"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0369"},{"key":"e_1_2_7_21_1","volume-title":"3,5\u2010Diiodothyropropionic acid (DITPA) in the Treatment of Patients with MCT8 Deficiency: A Preliminary Study","author":"Hameed S.","year":"2009"},{"key":"e_1_2_7_22_1","first-page":"4","volume-title":"Allan\u2010Herndon\u2010Dudley Syndrome: T3\/T4 Screening for Males with Mental Retardation of Unknown Etiology","author":"Rogers C.","year":"2008"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1501"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.208"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-006-0162-9"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcen.12023","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.12023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T08:10:04Z","timestamp":1697616604000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.12023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,7]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["10.1111\/cen.12023"],"URL":"https:\/\/doi.org\/10.1111\/cen.12023","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,7]]}}}