{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:22:59Z","timestamp":1783102979729,"version":"3.54.6"},"reference-count":42,"publisher":"Akademiai Kiado Zrt.","issue":"2","content-domain":{"domain":["akjournals.com"],"crossmark-restriction":true},"short-container-title":["PhysInt"],"published-print":{"date-parts":[[2022,6,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n            <jats:p>Congenital hypothyroidism (CH) occurs with a relatively alarming prevalence in infants, and if not diagnosed and treated in time, it can have devastating consequences for the development of the nervous system. CH is associated with genetic changes in several genes that encode transcription factors responsible for thyroid development, including mutations in the NK2 homeobox 1 (<jats:italic>NKX2.1<\/jats:italic>) gene, which encodes the thyroid transcription factor-1 (TTF-1). Although CH is frequently observed in pediatric populations, there is still a limited understanding of the genetic factors and molecular mechanisms contributing to this disease. The sequence of the <jats:italic>NKX2.1<\/jats:italic> gene was investigated in 75 pediatric patients with CH by polymerase chain reaction (PCR), single-stranded conformation polymorphism (SSCP), and direct DNA sequencing. Four missense heterozygous variations were identified in exon 3 of the <jats:italic>NKX2.1<\/jats:italic> gene, including three novel missense variations, namely c.708A&gt;G, p.Gln202Arg; c.713T&gt;G, p.Tyr204Asp; c.833T&gt;G, p.Tyr244Asp, and a previously reported variant rs781133468 (c.772C&gt;G, p.His223Gln). Importantly, these variations occur in highly conserved residues of the TTF-1 DNA-binding domain and were predicted by bioinformatics analysis to alter the protein structure, with a probable alteration in the protein function. These results indicate that nucleotide changes in the <jats:italic>NKX2.1<\/jats:italic> gene may contribute to CH pathogenesis.<\/jats:p>","DOI":"10.1556\/2060.2022.00224","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T13:34:13Z","timestamp":1654608853000},"page":"261-277","update-policy":"https:\/\/doi.org\/10.1556\/policypage.crossmark.crossref.1","source":"Crossref","is-referenced-by-count":1,"title":["Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH)"],"prefix":"10.1556","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-4746","authenticated-orcid":true,"given":"Mohammad Mehdi","family":"Heidari","sequence":"first","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Ali","family":"Madani Manshadi","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Reza","family":"Eshghi","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Talebi","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehri","family":"Khatami","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Bragan\u00e7a","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Biomedical Sciences, Algarve Biomedical Centre Research Institute, University of Algarve, Faro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Ordooei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyhane","family":"Chamani","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Department of Biology, Yazd University, Yazd, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"425","reference":[{"key":"B1","series-title":"Thyroid diseases: pathogenesis, diagnosis and treatment","first-page":"1","article-title":"Congenital hypothyroidism","author":"Di Cosmo \n                     C","year":"2018","unstructured":"Di Cosmo \n                     C\n                  , \n                     Tonacchera \n                     M\n                  \n               . 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Pediatr Neonatol \n               2017; 58(5): 442\u2013448. https:\/\/doi.org\/10.1016\/j.pedneo.2017.01.002.10.1016\/j.pedneo.2017.01.002"},{"issue":"3","key":"B9","series-title":"Horm Res Paediatr","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1159\/000448658","article-title":"Transient versus permanent congenital hypothyroidism after the age of 3 Years in infants detected on the first versus second newborn screening test in Oregon, USA","volume":"86","author":"Ford \n                     GA","year":"2016","unstructured":"Ford \n                     GA\n                  , \n                     Denniston \n                     S\n                  , \n                     Sesser \n                     D\n                  , \n                     Skeels \n                     MR\n                  , \n                     LaFranchi \n                     SH\n                  \n               . Transient versus permanent congenital hypothyroidism after the age of 3 Years in infants detected on the first versus second newborn screening test in Oregon, USA. Horm Res Paediatr \n               2016; 86(3): 169\u2013177. https:\/\/doi.org\/10.1159\/000448658.10.1159\/000448658"},{"issue":"6","key":"B10","series-title":"Endocrinology","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1210\/endo.143.6.8864","article-title":"Perspective: genetic defects in the etiology of congenital hypothyroidism","volume":"143","author":"Kopp \n                     P","year":"2002","unstructured":"Kopp \n                     P\n                  \n               . Perspective: genetic defects in the etiology of congenital hypothyroidism. 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