{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T02:00:30Z","timestamp":1789178430205,"version":"build-2803163510"},"reference-count":108,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health USA","doi-asserted-by":"publisher","award":["R37DK15070"],"award-info":[{"award-number":["R37DK15070"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Seymour J. Abrams Fund for Thyroid Research"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Best Practice &amp; Research Clinical Endocrinology &amp; Metabolism"],"published-print":{"date-parts":[[2017,3]]},"DOI":"10.1016\/j.beem.2017.03.004","type":"journal-article","created":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T17:46:33Z","timestamp":1490895993000},"page":"183-194","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":52,"title":["Resistance to thyrotropin"],"prefix":"10.1016","volume":"31","author":[{"given":"Helmut","family":"Grasberger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Refetoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.beem.2017.03.004_bib1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1210\/er.2012-1072","article-title":"Novel insights on thyroid-stimulating hormone receptor signal transduction","volume":"34","author":"Kleinau","year":"2013","journal-title":"Endocr Rev"},{"key":"10.1016\/j.beem.2017.03.004_bib2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/ncpendmet0401","article-title":"Technology insight: modern methods to monitor protein-protein interactions reveal functional TSH receptor oligomerization","volume":"3","author":"Persani","year":"2007","journal-title":"Nat Clin Pract Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1056\/NEJM199501193320305","article-title":"Brief report \u2013 resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene","volume":"332","author":"Sunthornthepvarakul","year":"1995","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.beem.2017.03.004_bib4","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/j.1365-2265.2010.03849.x","article-title":"Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism","volume":"73","author":"Cangul","year":"2010","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib5","first-page":"731","article-title":"A\u00a0deletion including exon 2 of the TSHR gene is associated with thyroid dysgenesis and severe congenital hypothyroidism","volume":"27","author":"Cangul","year":"2014","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib6","first-page":"171","article-title":"Identification of deletions in children with congenital hypothyroidism and thyroid dysgenesis with the use of multiplex ligation-dependent probe amplification","volume":"28","author":"Kumorowicz-Czoch","year":"2015","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib7","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1172\/JCI119497","article-title":"Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland","volume":"99","author":"Abramowicz","year":"1997","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.beem.2017.03.004_bib8","first-page":"3471","article-title":"Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism","volume":"82","author":"Biebermann","year":"1997","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib9","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/j.1365-2265.2007.02950.x","article-title":"Identification of TSH receptor mutations in three families with resistance to TSH","volume":"67","author":"Tonacchera","year":"2007","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib10","doi-asserted-by":"crossref","first-page":"E156","DOI":"10.1210\/jc.2011-1938","article-title":"Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia","volume":"97","author":"Calebiro","year":"2012","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib11","doi-asserted-by":"crossref","first-page":"5787","DOI":"10.1210\/jc.2004-1243","article-title":"Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism","volume":"89","author":"Tonacchera","year":"2004","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib12","doi-asserted-by":"crossref","first-page":"4543","DOI":"10.1210\/jcem.86.9.7791","article-title":"Thyroid resistance to TSH complicated by autoimmune thyroiditis","volume":"86","author":"Tonacchera","year":"2001","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib13","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1365-2265.2005.02314.x","article-title":"Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes","volume":"63","author":"Camilot","year":"2005","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib14","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1210\/jc.2009-0375","article-title":"Subclinical hypothyroidism in children and adolescents: a wide range of clinical, biochemical, and genetic factors involved","volume":"94","author":"Rapa","year":"2009","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib15","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.1210\/jc.2009-0618","article-title":"Thyrotropin-stimulating hormone receptor gene analysis in pediatric patients with non-autoimmune subclinical hypothyroidism","volume":"94","author":"Nicoletti","year":"2009","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib16","doi-asserted-by":"crossref","first-page":"E1340","DOI":"10.1210\/jc.2011-0070","article-title":"Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake","volume":"96","author":"Narumi","year":"2011","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib17","first-page":"1771","article-title":"Apparent congenital athyreosis contrasting with normal plasma thyroglobulin levels and associated with inactivating mutations in the thyrotropin receptor gene: are athyreosis and ectopic thyroid distinct entities?","volume":"83","author":"Gagne","year":"1998","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib18","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1210\/jcem.87.6.8536","article-title":"Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism","volume":"87","author":"Alberti","year":"2002","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib19","first-page":"4229","article-title":"Four families with loss of function mutations of the thyrotropin receptor","volume":"81","author":"deRoux","year":"1996","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib20","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1089\/thy.2006.16.1303","article-title":"A\u00a0novel mutation in the thyrotropin (thyroid-stimulating hormone) receptor gene in a case of congenital hypothyroidism","volume":"16","author":"Jeziorowska","year":"2006","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib21","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1507\/endocrj.K07E-064","article-title":"Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism","volume":"55","author":"Yuan","year":"2008","journal-title":"Endocr J"},{"key":"10.1016\/j.beem.2017.03.004_bib22","first-page":"1094","article-title":"Two novel mutations in the thyrotropin (TSH) receptor gene in a child with resistance to TSH","volume":"82","author":"CliftonBligh","year":"1997","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib23","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1210\/jc.2002-021301","article-title":"The W546X mutation of the thyrotropin receptor gene: potential major contributor to thyroid dysfunction in a Caucasian population","volume":"88","author":"Jordan","year":"2003","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/j.1365-2265.2004.01967.x","article-title":"Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor","volume":"60","author":"Park","year":"2004","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib25","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1089\/thy.1999.9.887","article-title":"The hypothyroidism in an inbred kindred with congenital thyroid hormone and glucocorticoid deficiency is due to a mutation producing a truncated thyrotropin receptor","volume":"9","author":"Tiosano","year":"1999","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib26","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1089\/thy.2004.14.971","article-title":"Congenital primary hypothyroidism in a Turkish family caused by a homozygous nonsense mutation (R609X) in the thyrotropin receptor gene","volume":"14","author":"Richter-Unruh","year":"2004","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1442-200x.2005.02020.x","article-title":"Subclinical hypothyroidism caused by a mutation of the thyrotropin receptor gene","volume":"47","author":"Shibayama","year":"2005","journal-title":"Pediatr Int"},{"key":"10.1016\/j.beem.2017.03.004_bib28","first-page":"419","article-title":"TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis","volume":"25","author":"Cangul","year":"2012","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib29","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1089\/105072501753211064","article-title":"A\u00a0familial case of congenital hypothyroidism caused by a homozygous mutation of the thyrotropin receptor gene","volume":"11","author":"Bretones","year":"2001","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1089\/thy.2010.0187","article-title":"A\u00a0family with congenital hypothyroidism caused by a combination of loss-of-function mutations in the thyrotropin receptor and adenylate cyclase-stimulating g alpha-protein subunit genes","volume":"21","author":"Lado-Abeal","year":"2011","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib31","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1210\/jc.2008-1938","article-title":"Loss-of-function mutations in the thyrotropin receptor gene as a major determinant of hyperthyrotropinemia in a consanguineous community","volume":"94","author":"Tenenbaum-Rakover","year":"2009","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib32","doi-asserted-by":"crossref","first-page":"E1001","DOI":"10.1210\/jc.2011-0127","article-title":"The coexistence of a novel inactivating mutant thyrotropin receptor allele with two thyroid peroxidase mutations: a genotype-phenotype correlation","volume":"96","author":"Sriphrapradang","year":"2011","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib33","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1210\/jc.2008-1767","article-title":"TSHR mutations as a cause of congenital hypothyroidism in Japan: a population-based genetic epidemiology study","volume":"94","author":"Narumi","year":"2009","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib34","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.1365-2265.2011.04156.x","article-title":"Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism","volume":"75","author":"Lee","year":"2011","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib35","first-page":"4238","article-title":"A\u00a0novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH","volume":"85","author":"Russo","year":"2000","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib36","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1089\/105072501750302859","article-title":"Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin","volume":"11","author":"Nagashima","year":"2001","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib37","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s12020-006-0018-z","article-title":"Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese","volume":"30","author":"Kanda","year":"2006","journal-title":"Endocrine"},{"key":"10.1016\/j.beem.2017.03.004_bib38","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1089\/thy.2006.16.471","article-title":"Identification and functional analysis of novel inactivating thyrotropin receptor mutations in patients with thyrotropin resistance","volume":"16","author":"Tsunekawa","year":"2006","journal-title":"Thyroid"},{"key":"10.1016\/j.beem.2017.03.004_bib39","first-page":"1001","article-title":"Congenital hypothyroidism with impaired thyroid response to thyrotropin (TSH) and absent circulating thyroglobulin: evidence for a new inactivating mutation of the TSH receptor gene","volume":"85","author":"Tonacchera","year":"2000","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib40","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1210\/en.2008-1145","article-title":"An inactivating mutation within the first extracellular loop of the thyrotropin receptor impedes normal posttranslational maturation of the extracellular domain","volume":"150","author":"Sura-Trueba","year":"2009","journal-title":"Endocrinology"},{"key":"10.1016\/j.beem.2017.03.004_bib41","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1055\/s-2005-865914","article-title":"Mild congenital primary hypothyroidism in a Turkish family caused by a homozygous missense thyrotropin receptor (TSHR) gene mutation (A593 V)","volume":"113","author":"Fricke-Otto","year":"2005","journal-title":"Exp Clin Endocr Diab"},{"key":"10.1016\/j.beem.2017.03.004_bib42","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1515\/jpem-2012-0308","article-title":"Novel heterozygous thyrotropin receptor mutation presenting with neonatal hyperthyrotropinaemia, mild thyroid hypoplasia and absent uptake on radioisotope scan","volume":"26","author":"Lucas-Herald","year":"2013","journal-title":"J\u00a0Pediatr Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib43","first-page":"716","article-title":"The W520X mutation in the TSHR gene brings on subclinical hypothyroidism through an haploinsufficiency mechanism","volume":"36","author":"Moia","year":"2013","journal-title":"J\u00a0Endocrinol Invest"},{"key":"10.1016\/j.beem.2017.03.004_bib44","first-page":"1021","article-title":"An essential splice site mutation (c.317+1G > A) in the TSHR gene leads to severe thyroid dysgenesis","volume":"27","author":"Cangul","year":"2014","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib45","first-page":"1153","article-title":"Mild and severe congenital primary hypothyroidism in two patients by thyrotropin receptor (TSHR) gene mutation","volume":"25","author":"Bas","year":"2012","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib46","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.cca.2012.02.027","article-title":"R450H TSH receptor mutation in congenital hypothyroidism in Taiwanese children","volume":"413","author":"Chang","year":"2012","journal-title":"Clin Chim Acta"},{"key":"10.1016\/j.beem.2017.03.004_bib47","first-page":"1101","article-title":"A\u00a0nonsense thyrotropin receptor gene mutation (R609X) is associated with congenital hypothyroidism and heart defects","volume":"27","author":"Cangul","year":"2014","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib48","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1159\/000362235","article-title":"High frequency of DUOX2 mutations in transient or permanent congenital hypothyroidism with eutopic thyroid glands","volume":"82","author":"Jin","year":"2014","journal-title":"Horm Res Paediat"},{"key":"10.1016\/j.beem.2017.03.004_bib49","doi-asserted-by":"crossref","first-page":"964635","DOI":"10.1155\/2014\/964635","article-title":"Frequency and clinical implication of the R450H mutation in the thyrotropin receptor gene in the Japanese population detected by smart amplification process 2","volume":"2014","author":"Tsunekawa","year":"2014","journal-title":"Biomed Res Int"},{"key":"10.1016\/j.beem.2017.03.004_bib50","first-page":"657","article-title":"Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene","volume":"28","author":"Satoh","year":"2015","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib51","first-page":"777","article-title":"Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion","volume":"28","author":"Cerqueira","year":"2015","journal-title":"J\u00a0Pediatr Endocr Met"},{"key":"10.1016\/j.beem.2017.03.004_bib52","doi-asserted-by":"crossref","first-page":"E1039","DOI":"10.1210\/jc.2014-4511","article-title":"Loss-of-function variants in a Hungarian cohort reveal structural insights on TSH receptor maturation and signaling","volume":"100","author":"Labadi","year":"2015","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib53","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.cca.2016.09.007","article-title":"Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients","volume":"462","author":"Fu","year":"2016","journal-title":"Clin Chim Acta"},{"key":"10.1016\/j.beem.2017.03.004_bib54","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3109\/07435800.2015.1124438","article-title":"Two novel TSHR gene mutations (p.R528C and c.392+4del4) associated with congenital hypothyroidism","volume":"41","author":"Qiu","year":"2016","journal-title":"Endocr Res"},{"key":"10.1016\/j.beem.2017.03.004_bib55","doi-asserted-by":"crossref","first-page":"2816","DOI":"10.1210\/jc.2007-0366","article-title":"A\u00a0familial thyrotropin (TSH) receptor mutation provides in\u00a0vivo evidence that the inositol phosphates\/Ca(2+) cascade mediates TSH action on thyroid hormone synthesis","volume":"92","author":"Grasberger","year":"2007","journal-title":"J\u00a0Clin Endocr Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib56","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1210\/en.2011-0204","article-title":"Minireview: intrinsic and extrinsic factors in thyroid gland development: an update","volume":"152","author":"De Felice","year":"2011","journal-title":"Endocrinology"},{"key":"10.1016\/j.beem.2017.03.004_bib57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.mce.2014.08.004","article-title":"The paired box transcription factor PAX8 is essential for function and survival of adult thyroid cells","volume":"396","author":"Marotta","year":"2014","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib58","doi-asserted-by":"crossref","first-page":"e729","DOI":"10.1038\/cddis.2013.262","article-title":"PAX8 has a critical role in epithelial cell survival and proliferation","volume":"4","author":"Di Palma","year":"2013","journal-title":"Cell Death Dis"},{"key":"10.1016\/j.beem.2017.03.004_bib59","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/ng0598-87","article-title":"Follicular cells of the thyroid gland require PAX8 gene function","volume":"19","author":"Mansouri","year":"1998","journal-title":"Nat Genet"},{"key":"10.1016\/j.beem.2017.03.004_bib60","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nature11525","article-title":"Generation of functional thyroid from embryonic stem cells","volume":"491","author":"Antonica","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.beem.2017.03.004_bib61","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/ng0598-83","article-title":"PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis","volume":"19","author":"Macchia","year":"1998","journal-title":"Nat Genet"},{"key":"10.1016\/j.beem.2017.03.004_bib62","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1590\/S0004-27302010000600008","article-title":"Mutations in the gene encoding paired box domain (PAX8) are not a frequent cause of congenital hypothyroidism (CH) in Iranian patients with thyroid dysgenesis","volume":"54","author":"Mahjoubi","year":"2010","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"10.1016\/j.beem.2017.03.004_bib63","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1590\/S0004-27302012000300004","article-title":"Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis","volume":"56","author":"Brust","year":"2012","journal-title":"Arq Bras Endocrinol Metabol"},{"key":"10.1016\/j.beem.2017.03.004_bib64","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1530\/EJE-06-0709","article-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","volume":"156","author":"Al Taji","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib65","first-page":"889","article-title":"Screening of PAX8 mutations in Chinese patients with congenital hypothyroidism","volume":"35","author":"Liu","year":"2012","journal-title":"J\u00a0Endocrinol Invest"},{"key":"10.1016\/j.beem.2017.03.004_bib66","first-page":"96","article-title":"Screening for PAX8 mutations in patients with congenital hypothyroidism in south-west Germany","volume":"66","author":"Lanzerath","year":"2006","journal-title":"Horm Res"},{"key":"10.1016\/j.beem.2017.03.004_bib67","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1530\/EJE-13-1006","article-title":"Extreme phenotypic variability of thyroid dysgenesis in six new cases of congenital hypothyroidism due to PAX8 gene loss-of-function mutations","volume":"171","author":"Ramos","year":"2014","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib68","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1515\/jpem-2014-0310","article-title":"Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands","volume":"28","author":"Kumorowicz-Czoch","year":"2015","journal-title":"J\u00a0Pediatr Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib69","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1089\/gte.2007.0033","article-title":"Implementation of a congenital hypothyroidism newborn screening procedure with mutation detection on genomic DNA extracted from blood spots: the experience of the Italian northeastern reference center","volume":"11","author":"Camilot","year":"2007","journal-title":"Genet Test"},{"key":"10.1016\/j.beem.2017.03.004_bib70","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1089\/thy.2012.0141","article-title":"Two cases of thyroid dysgenesis caused by different novel PAX8 mutations in the DNA-binding region: in\u00a0vitro studies reveal different pathogenic mechanisms","volume":"23","author":"Hermanns","year":"2013","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib71","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1515\/jpem-2015-0199","article-title":"Analysis of the PAX8 gene in 32 children with thyroid dysgenesis and functional characterization of a promoter variant","volume":"29","author":"Perone","year":"2016","journal-title":"J\u00a0Pediatr Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib72","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1530\/EJE-12-0410","article-title":"Functional characterization of four novel PAX8 mutations causing congenital hypothyroidism: new evidence for haploinsufficiency as a disease mechanism","volume":"167","author":"Narumi","year":"2012","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib73","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1089\/thy.2012.0357","article-title":"Functional analysis of the murine PAX8 promoter reveals autoregulation and the presence of a novel thyroid-specific DNA-binding activity","volume":"23","author":"di Gennaro","year":"2013","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib74","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1067\/mpd.2001.117071","article-title":"Thyroid dysgenesis caused by PAX8 mutation: the hypermutability with CPG dinucleotides at codon 31","volume":"139","author":"Komatsu","year":"2001","journal-title":"J\u00a0Pediatr"},{"key":"10.1016\/j.beem.2017.03.004_bib75","first-page":"619013","article-title":"Congenital hypothyroidism caused by a PAX8 gene mutation manifested as sodium\/iodide symporter gene defect","volume":"2010","author":"Jo","year":"2010","journal-title":"J\u00a0Thyroid Res"},{"key":"10.1016\/j.beem.2017.03.004_bib76","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.cca.2015.09.008","article-title":"PAX8 pathogenic variants in Chinese patients with congenital hypothyroidism","volume":"450","author":"Fu","year":"2015","journal-title":"Clin Chim Acta \u2013 Int J Clin Chem"},{"key":"10.1016\/j.beem.2017.03.004_bib77","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1089\/thy.2016.0016","article-title":"Detection of novel gene variants associated with congenital hypothyroidism in a Finnish patient cohort","volume":"26","author":"Lof","year":"2016","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib78","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1210\/me.2004-0426","article-title":"Thyroid transcription factor 1 rescues PAX8\/p300 synergism impaired by a natural PAX8 paired domain mutation with dominant negative activity","volume":"19","author":"Grasberger","year":"2005","journal-title":"Mol Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib79","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1365-2265.2007.02831.x","article-title":"Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant","volume":"67","author":"Tonacchera","year":"2007","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib80","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/j.1365-2265.2010.03851.x","article-title":"Characterization of a novel loss-of-function mutation of PAX8 associated with congenital hypothyroidism","volume":"73","author":"Di Palma","year":"2010","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib81","first-page":"234","article-title":"Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8","volume":"86","author":"Vilain","year":"2001","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib82","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1210\/jcem.86.8.7765","article-title":"A\u00a0novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child","volume":"86","author":"Congdon","year":"2001","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib83","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.1210\/jc.2004-0398","article-title":"Familial PAX8 small deletion (c.989_992delACCC) associated with extreme phenotype variability","volume":"89","author":"de Sanctis","year":"2004","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib84","doi-asserted-by":"crossref","first-page":"E2039","DOI":"10.1210\/jc.2011-1114","article-title":"PAX8 mutation disturbing thyroid follicular growth: a case report","volume":"96","author":"Narumi","year":"2011","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib85","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1210\/jc.2004-0166","article-title":"Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid","volume":"89","author":"Meeus","year":"2004","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib86","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1210\/jc.2009-2373","article-title":"Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients","volume":"95","author":"Narumi","year":"2010","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib87","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1101\/gad.240102","article-title":"Nephric lineage specification by PAX2 and PAX8","volume":"16","author":"Bouchard","year":"2002","journal-title":"Genes Dev"},{"key":"10.1016\/j.beem.2017.03.004_bib88","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1089\/thy.2012.0649","article-title":"A\u00a0new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract","volume":"23","author":"Carvalho","year":"2013","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib89","doi-asserted-by":"crossref","first-page":"4025","DOI":"10.1210\/jc.2005-0572","article-title":"Autosomal dominant resistance to thyrotropin as a distinct entity in five multigenerational kindreds: clinical characterization and exclusion of candidate loci","volume":"90","author":"Grasberger","year":"2005","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib90","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s00439-005-0036-6","article-title":"Identification of a locus for nongoitrous congenital hypothyroidism on chromosome 15q25.3\u201326.1","volume":"118","author":"Grasberger","year":"2005","journal-title":"Hum Genet"},{"key":"10.1016\/j.beem.2017.03.004_bib91","doi-asserted-by":"crossref","first-page":"e1003266","DOI":"10.1371\/journal.pgen.1003266","article-title":"A\u00a0meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function","volume":"9","author":"Porcu","year":"2013","journal-title":"PLoS Genet"},{"key":"10.1016\/j.beem.2017.03.004_bib92","doi-asserted-by":"crossref","first-page":"e111301","DOI":"10.1371\/journal.pone.0111301","article-title":"Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the emerge network","volume":"9","author":"Malinowski","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.beem.2017.03.004_bib93","first-page":"675","article-title":"Endocrine manifestations of stimulatory g protein alpha-subunit mutations and the role of genomic imprinting","volume":"22","author":"Weinstein","year":"2001","journal-title":"Endocr Rev"},{"key":"10.1016\/j.beem.2017.03.004_bib94","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1056\/NEJM199804303381817","article-title":"Deletion of thyroid transcription factor-1 gene in an infant with neonatal thyroid dysfunction and respiratory failure","volume":"338","author":"Devriendt","year":"1998","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.beem.2017.03.004_bib95","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1172\/JCI0214341","article-title":"Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency","volume":"109","author":"Krude","year":"2002","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.beem.2017.03.004_bib96","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1172\/JCI0214192","article-title":"Partial deficiency of thyroid transcription factor 1 produces predominantly neurological defects in humans and mice","volume":"109","author":"Pohlenz","year":"2002","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.beem.2017.03.004_bib97","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1007\/s12311-014-0570-7","article-title":"A\u00a0novel de novo mutation of the TITF1\/NKX2-1 gene causing ataxia, benign hereditary chorea, hypothyroidism and a pituitary mass in a UK family and review of the literature","volume":"13","author":"Veneziano","year":"2014","journal-title":"Cerebellum"},{"key":"10.1016\/j.beem.2017.03.004_bib98","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1093\/hmg\/ddp162","article-title":"Five new TTF1\/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case","volume":"18","author":"Carre","year":"2009","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.beem.2017.03.004_bib99","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1530\/EJE-15-0959","article-title":"Natural course of congenital hypothyroidism by dual oxidase 2 mutations from the neonatal period through puberty","volume":"174","author":"Maruo","year":"2016","journal-title":"Eur J Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib100","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.cca.2016.04.019","article-title":"Next-generation sequencing analysis of DUOX2 in 192 Chinese subclinical congenital hypothyroidism (SCH) and ch patients","volume":"458","author":"Fu","year":"2016","journal-title":"Clin Chim Acta \u2013 Int J Clin Chem"},{"key":"10.1016\/j.beem.2017.03.004_bib101","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3343\/alm.2016.36.2.145","article-title":"DUOX2 mutations are frequently associated with congenital hypothyroidism in the Korean population","volume":"36","author":"Park","year":"2016","journal-title":"Ann Lab Med"},{"key":"10.1016\/j.beem.2017.03.004_bib102","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1089\/thy.2016.0469","article-title":"DUOX2 gene mutation manifesting as resistance to thyrotropin phenotype","volume":"27","author":"Srichomkwun","year":"2017","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib103","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.mce.2010.01.029","article-title":"Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism","volume":"322","author":"Grasberger","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.beem.2017.03.004_bib104","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1089\/thy.2013.0164","article-title":"Analysis of the thyroid phenotype in 42 patients with Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct","volume":"24","author":"Ladsous","year":"2014","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib105","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1210\/jc.2010-0228","article-title":"A\u00a0coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid","volume":"95","author":"Senou","year":"2010","journal-title":"J\u00a0Clin Endocrinol Metab"},{"key":"10.1016\/j.beem.2017.03.004_bib106","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1089\/thy.2014.0311","article-title":"Long-term outcome of loss-of-function mutations in thyrotropin receptor gene","volume":"25","author":"Tenenbaum-Rakover","year":"2015","journal-title":"Thyroid \u2013 Off J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2017.03.004_bib107","first-page":"318","article-title":"Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene","volume":"71","author":"Mizuno","year":"2009","journal-title":"Horm Res"},{"key":"10.1016\/j.beem.2017.03.004_bib108","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1111\/j.1432-1033.1997.00860.x","article-title":"Determination of functional domains of the human transcription factor PAX8 responsible for its nuclear localization and transactivating potential","volume":"247","author":"Poleev","year":"1997","journal-title":"Eur J Biochem"}],"container-title":["Best Practice &amp; Research Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521690X17300106?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521690X17300106?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T16:52:50Z","timestamp":1761497570000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1521690X17300106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3]]},"references-count":108,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017,3]]}},"alternative-id":["S1521690X17300106"],"URL":"https:\/\/doi.org\/10.1016\/j.beem.2017.03.004","relation":{},"ISSN":["1521-690X"],"issn-type":[{"value":"1521-690X","type":"print"}],"subject":[],"published":{"date-parts":[[2017,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Resistance to thyrotropin","name":"articletitle","label":"Article Title"},{"value":"Best Practice & Research Clinical Endocrinology & Metabolism","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.beem.2017.03.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2017 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}