{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:24:32Z","timestamp":1778768672270,"version":"3.51.4"},"reference-count":46,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"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 & Research Clinical Endocrinology & Metabolism"],"published-print":{"date-parts":[[2018,8]]},"DOI":"10.1016\/j.beem.2018.05.002","type":"journal-article","created":{"date-parts":[[2018,5,19]],"date-time":"2018-05-19T07:54:33Z","timestamp":1526716473000},"page":"387-396","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":66,"title":["Genetics and management of congenital hypothyroidism"],"prefix":"10.1016","volume":"32","author":[{"given":"Luca","family":"Persani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuditta","family":"Rurale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziana","family":"de Filippis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Galazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Muzza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Fugazzola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.beem.2018.05.002_bib1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1210\/jc.2013-1891","article-title":"European society for paediatric endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism","volume":"99","author":"L\u00e9ger","year":"2014","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib2","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1111\/j.1365-2265.2009.03568.x","article-title":"A\u00a07-year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH)","volume":"71","author":"Corbetta","year":"2009","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2018.05.002_bib3","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1210\/jc.2012-3273","article-title":"Italian Study Group for Congenital Hypothyroidism. Congenital hypothyroidism due to defects of thyroid development and mild increase of TSH at screening: data from the Italian National Registry of infants with congenital hypothyroidism","volume":"98","author":"Olivieri","year":"2013","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib4","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1210\/jc.2010-1711","article-title":"Congenital hypothyroidism: an evolving common clinical conundrum","volume":"95","author":"Rapaport","year":"2010","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3389\/fendo.2012.00018","article-title":"Congenital hypothyroidism with gland in situ is more frequent than previously thought","volume":"3","author":"Persani","year":"2012","journal-title":"Front Endocrinol (Lausanne)."},{"key":"10.1016\/j.beem.2018.05.002_bib6","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1210\/er.2003-0028","article-title":"Thyroid development and its disorders: genetics and molecular mechanisms","volume":"25","author":"De Felice","year":"2004","journal-title":"Endocr Rev"},{"key":"10.1016\/j.beem.2018.05.002_bib7","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.2018.05.002_bib8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1136\/jmg.2004.024158","article-title":"Genetics of congenital hypothyroidism","volume":"42","author":"Park","year":"2005","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.beem.2018.05.002_bib9","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1093\/hmg\/ddx145","article-title":"A\u00a0frequent oligogenic involvement in congenital hypothyroidism","volume":"26","author":"de Filippis","year":"2017","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.beem.2018.05.002_bib10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1210\/jc.2007-2020","article-title":"Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism","volume":"93","author":"Zamproni","year":"2008","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.beem.2017.04.007","article-title":"The role of GLIS3 in thyroid disease as part of a multisystem disorder","volume":"31","author":"Dimitri","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib12","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1056\/NEJMoa0706819","article-title":"Mutations in the iodotyrosine deiodinase gene and hypothyroidism","volume":"358","author":"Moreno","year":"2008","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.beem.2018.05.002_bib13","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1210\/jc.2015-3403","article-title":"JAG1 Loss-of-function variations as a novel predisposing event in the pathogenesis of congenital thyroid defects","volume":"101","author":"de Filippis","year":"2016","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib14","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1136\/jmedgenet-2013-102248","article-title":"Comprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum","volume":"51","author":"Thorwarth","year":"2014","journal-title":"J\u00a0Med Genet"},{"key":"10.1016\/j.beem.2018.05.002_bib15","doi-asserted-by":"crossref","first-page":"E544","DOI":"10.1210\/jc.2013-3618","article-title":"The clinical and molecular characterization of patients with dyshormonogenic congenital hypothyroidism reveals specific diagnostic clues for DUOX2 defects","volume":"99","author":"Muzza","year":"2014","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mce.2010.01.008","article-title":"Genetics and phenomics of hypothyroidism due to TSH resistance","volume":"322","author":"Persani","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.beem.2018.05.002_bib17","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 Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib18","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nature08494","article-title":"Finding the missing heritability of complex diseases","volume":"461","author":"Manolio","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.beem.2018.05.002_bib19","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1056\/NEJMp1400788","article-title":"Genotype\u2013phenotype correlation-promiscuity in the era of next-generation sequencing","volume":"371","author":"Lu","year":"2014","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.beem.2018.05.002_bib20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/jcem.87.2.8268","article-title":"Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism","volume":"87","author":"L\u00e9ger","year":"2002","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.beem.2017.04.008","article-title":"Disorders of thyroid morphogenesis","volume":"31","author":"Abu-Khudir","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib22","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1210\/jc.2004-1358","article-title":"PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations","volume":"90","author":"Trueba","year":"2005","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib23","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.2018.05.002_bib24","first-page":"227","article-title":"Novel NKX2-1 frameshift mutations in patients with atypical phenotypes of the brain-lung-thyroid syndrome","volume":"3","author":"de Filippis","year":"2014","journal-title":"Eur Thyroid J"},{"key":"10.1016\/j.beem.2018.05.002_bib25","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.2018.05.002_bib26","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.mce.2010.03.009","article-title":"Genetics and phenomics of hypothyroidism and thyroid dys- and agenesis due to PAX8 and TTF1 mutations","volume":"322","author":"Montanelli","year":"2010","journal-title":"Mol Cell Endocrinol"},{"key":"10.1016\/j.beem.2018.05.002_bib27","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 Offic J Am Thyroid Assoc"},{"key":"10.1016\/j.beem.2018.05.002_bib28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s00439-007-0420-5","article-title":"Polymorphic length of FOXE1 alanine stretch: evidence for genetic susceptibility to thyroid dysgenesis","volume":"122","author":"Carre","year":"2007","journal-title":"Hum Genet"},{"key":"10.1016\/j.beem.2018.05.002_bib29","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1210\/jc.2005-1350","article-title":"Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis","volume":"91","author":"Dentice","year":"2006","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib30","doi-asserted-by":"crossref","first-page":"e52685","DOI":"10.1371\/journal.pone.0052685","article-title":"The ambiguous role of NKX2-5 mutations in thyroid dysgenesis","volume":"7","author":"van Engelen","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.beem.2018.05.002_bib31","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s40618-017-0715-x","article-title":"Role of Jagged1-Notch pathway in thyroid development","volume":"41","author":"Marelli","year":"2018","journal-title":"J\u00a0Endocrinol Invest"},{"key":"10.1016\/j.beem.2018.05.002_bib32","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.beem.2017.04.004","article-title":"Hypothyroidism associated with parathyroid disorders","volume":"31","author":"Mantovani","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib33","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.beem.2017.03.004","article-title":"Resistance to thyrotropin","volume":"31","author":"Grasberger","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib34","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/cen.13387","article-title":"Mild TSH resistance: clinical and hormonal features in childhood and adulthood","volume":"87","author":"Vigone","year":"2017","journal-title":"Clin Endocrinol"},{"key":"10.1016\/j.beem.2018.05.002_bib35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.beem.2017.04.011","article-title":"Pendred syndrome","volume":"31","author":"W\u00e9meau","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib36","first-page":"2469","article-title":"Molecular analysis of the Pendred's syndrome gene and magnetic resonance imaging studies of the inner ear are essential for the diagnosis of true Pendred's syndrome","volume":"85","author":"Fugazzola","year":"2000","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib37","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.beem.2017.03.006","article-title":"Iodide handling disorders (NIS, TPO, TG, IYD)","volume":"31","author":"Targovnik","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib38","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.beem.2017.04.006","article-title":"Disorders of H2O2 generation","volume":"31","author":"Muzza","year":"2017","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib39","doi-asserted-by":"crossref","first-page":"849","DOI":"10.7754\/Clin.Lab.2015.150840","article-title":"Heterozygous mutations of the DUOXA2 and DUOX2 genes in dizygotic twins with congenital hypothyroidism","volume":"62","author":"Yang","year":"2016","journal-title":"Clin Lab"},{"key":"10.1016\/j.beem.2018.05.002_bib40","doi-asserted-by":"crossref","first-page":"E841","DOI":"10.1210\/jc.2010-2321","article-title":"A\u00a0single copy of the recently identified dual oxidase maturation factor (DUOXA) 1 gene produces only mild transient hypothyroidism in a patient with a novel biallelic DUOXA2 mutation and monoallelic DUOXA1 deletion","volume":"96","author":"Hulur","year":"2011","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4274\/jcrpe.2380","article-title":"A\u00a0novel c.554+5C>T mutation in the DUOXA2 gene combined with p.R885Q mutation in the DUOX2 gene causing congenital hypothyroidism","volume":"8","author":"Zheng","year":"2016","journal-title":"J\u00a0Clin Res Pediatric Endocrinol"},{"key":"10.1016\/j.beem.2018.05.002_bib42","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1210\/jc.2017-00529","article-title":"Digenic DUOX1 and DUOX2 mutations in cases with congenital hypothyroidism","volume":"102","author":"Aycan","year":"2017","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib43","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1210\/jc.2002-021377","article-title":"Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect","volume":"88","author":"Fugazzola","year":"2003","journal-title":"J\u00a0Clin Endocrinol Metabol"},{"key":"10.1016\/j.beem.2018.05.002_bib44","doi-asserted-by":"crossref","first-page":"5038","DOI":"10.1210\/en.2005-0882","article-title":"A\u00a0mouse model demonstrates a multigenic origin of congenital hypothyroidism","volume":"146","author":"Amendola","year":"2005","journal-title":"Endocrinology"},{"key":"10.1016\/j.beem.2018.05.002_bib45","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"},{"key":"10.1016\/j.beem.2018.05.002_bib46","doi-asserted-by":"crossref","first-page":"4521","DOI":"10.1210\/jc.2016-1879","article-title":"Comprehensive screening of eight known causative genes in congenital hypothyroidism with gland-in-situ","volume":"101","author":"Nicholas","year":"2016","journal-title":"J\u00a0Clin Endocrinol Metabol"}],"container-title":["Best Practice & Research Clinical Endocrinology & Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521690X18300708?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1521690X18300708?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T16:53:49Z","timestamp":1761497629000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1521690X18300708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["S1521690X18300708"],"URL":"https:\/\/doi.org\/10.1016\/j.beem.2018.05.002","relation":{},"ISSN":["1521-690X"],"issn-type":[{"value":"1521-690X","type":"print"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genetics and management of congenital hypothyroidism","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.2018.05.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}