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Membrane transporters are rate\u2010limiting for cellular entry of thyroid hormones (TH) (T4 and T3) into some tissues, with selenocysteine\u2010containing, deiodinase enzymes (DIO1 and\u00a0DIO2) converting T4 to the biologically active hormone T3. TH regulate expression of target genes via hormone\u2010inducible nuclear receptors (TR\u03b1 and\u00a0TR\u03b2) to exert their physiological effects. Primary congenital hypothyroidism (CH) due to thyroid dysgenesis may be mediated by defects in thyroid transcription factors or impaired thyroid stimulating hormone receptor function. Dyshormonogenic CH is usually due to mutations in genes mediating thyroidal iodide transport, organification or iodotyrosine synthesis and recycling. Disorders of TH signalling encompass conditions due to defects in membrane TH transporters, impaired hormone metabolism due to deficiency of deiodinases and syndromes of Resistance to thyroid hormone due to pathogenic variants in either TR\u03b1 or TR\u03b2. Here, we review the genetic basis, pathogenesis and clinical features of congenital, dysgenetic or dyshormonogenic hypothyroidism and disorders of TH transport, metabolism and action.<\/jats:p>","DOI":"10.1111\/cen.14817","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T02:54:41Z","timestamp":1661309681000},"page":"502-514","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Genetic disorders of thyroid development, hormone biosynthesis\u00a0and signalling"],"prefix":"10.1111","volume":"97","author":[{"given":"Carla","family":"Moran","sequence":"first","affiliation":[{"name":"Wellcome Trust\u2010MRC Institute of Metabolic Science University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0847-2884","authenticated-orcid":false,"given":"Nadia","family":"Schoenmakers","sequence":"additional","affiliation":[{"name":"Wellcome Trust\u2010MRC Institute of Metabolic Science University of Cambridge Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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