{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T01:33:35Z","timestamp":1773797615084,"version":"3.50.1"},"reference-count":57,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Thyroid dyshormonogenesis is a heterogeneous group of hereditary diseases produced by a total\/partial blockage of the biochemical processes of thyroid-hormone synthesis and secretion. Paired box 8 (PAX8) is essential for thyroid morphogenesis and thyroid hormone synthesis. We aimed to identify PAX8 variants in patients with thyroid dyshormonogenesis and to analyze them with in vitro functional studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients and Methods<\/jats:title>\n                  <jats:p>Nine pediatric patients with a eutopic thyroid gland were analyzed by the Catalan screening program for congenital hypothyroidism. Scintigraphies showed absent, low, or normal uptake. Only one patient had a hypoplastic gland. On reevaluation, perchlorate discharge test was negative or compatible with partial iodine-organization deficit. After evaluation, 8 patients showed permanent mild or severe hypothyroidism. Massive-sequencing techniques were used to detect variants in congenital hypothyroidism-related genes. In vitro functional studies were based on transactivating activity of mutant PAX8 on a TG-gene promoter and analyzed by a dual-luciferase assays.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 7 heterozygous PAX8 exonic variants and 1 homozygous PAX8 splicing variant in 9 patients with variable phenotypes of thyroid dyshormonogenesis. Five were novel and 5 variants showed a statistically significant impaired transcriptional activity of TG promoter: 51% to 78% vs the wild type.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Nine patients presented with PAX8 candidate variants. All presented with a eutopic thyroid gland and 7 had deleterious variants. The phenotype of affected patients varies considerably, even within the same family; but, all except the homozygous patient presented with a normal eutopic thyroid gland and thyroid dyshormonogenesis. PAX8 functional studies have shown that 6 PAX8 variants are deleterious. Our studies have proven effective in evaluating these variants.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa711","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T05:25:09Z","timestamp":1602134709000},"page":"e152-e170","source":"Crossref","is-referenced-by-count":11,"title":["Phenotypic Variability of Patients With <i>PAX8<\/i> Variants Presenting With Congenital Hypothyroidism and Eutopic Thyroid"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-8201","authenticated-orcid":false,"given":"N\u00faria","family":"Camats","sequence":"first","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"CIBERER, ISCIII, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noelia","family":"Baz-Red\u00f3n","sequence":"additional","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Fern\u00e1ndez-Cancio","sequence":"additional","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"CIBERER, ISCIII, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Clemente","sequence":"additional","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"CIBERER, ISCIII, Madrid, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"},{"name":"Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariadna","family":"Campos-Martorell","sequence":"additional","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"},{"name":"Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadya","family":"Jaimes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Hospital Fundaci\u00f3n la Misericordia HOMI, Bogot\u00e1, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda","family":"Antol\u00edn","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Medicine Genetics Group, VHIR, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Garcia-Arum\u00ed","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Medicine Genetics Group, VHIR, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, VHIR, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Blasco-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"Medicine Genetics Group, VHIR, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Paramonov","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Disease, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard","family":"Mogas","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Soler-Colomer","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diego","family":"Yeste","sequence":"additional","affiliation":[{"name":"Growth and Development group, Vall d\u2019Hebron Research Institute (VHIR), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"},{"name":"CIBERER, ISCIII, Madrid, Spain"},{"name":"Pediatrics, Obstetrics and Gynecology and Preventive Medicine Department, Universitat Aut\u00f2noma de Barcelona, Bellaterra, Spain"},{"name":"Pediatric Endocrinology Section, Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"2021122204032692300_CIT0001","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1750-1172-5-17","article-title":"Congenital hypothyroidism","volume":"5","author":"Rastogi","year":"2010","journal-title":"Orphanet J Rare Dis."},{"issue":"3","key":"2021122204032692300_CIT0002","first-page":"200","article-title":"Genetics of primary congenital hypothyroidism","volume":"15","author":"Zwaveling-Soonawala","year":"2018","journal-title":"Pediatr Endocrinol Rev."},{"issue":"6","key":"2021122204032692300_CIT0003","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/j.1365-2265.2011.04128.x","article-title":"The increased incidence of congenital hypothyroidism: fact or fancy?","volume":"75","author":"Mitchell","year":"2011","journal-title":"Clin Endocrinol (Oxf)."},{"key":"2021122204032692300_CIT0004","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000363156","article-title":"Clinical genetics of congenital hypothyroidism","volume":"26","author":"Szinnai","year":"2014","journal-title":"Endocr Dev."},{"issue":"2","key":"2021122204032692300_CIT0005","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nrendo.2011.160","article-title":"Detection and treatment of congenital hypothyroidism","volume":"8","author":"Gr\u00fcters","year":"2011","journal-title":"Nat Rev Endocrinol."},{"issue":"1","key":"2021122204032692300_CIT0006","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/nrendo.2014.186","article-title":"Thyroid transcription factors in development, differentiation and disease","volume":"11","author":"Fern\u00e1ndez","year":"2015","journal-title":"Nat Rev Endocrinol."},{"issue":"2","key":"2021122204032692300_CIT0007","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1242\/dev.110.2.643","article-title":"Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland","volume":"110","author":"Plachov","year":"1990","journal-title":"Development."},{"key":"2021122204032692300_CIT0008","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1472-6823-14-69","article-title":"Identification of a novel PAX8 gene sequence variant in four members of the same family: from congenital hypothyroidism with thyroid hypoplasia to mild subclinical hypothyroidism","volume":"14","author":"Vincenzi","year":"2014","journal-title":"BMC Endocr Disord."},{"issue":"5","key":"2021122204032692300_CIT0009","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."},{"issue":"24","key":"2021122204032692300_CIT0010","doi-asserted-by":"crossref","first-page":"13144","DOI":"10.1073\/pnas.240336397","article-title":"Pax8 has a key role in thyroid cell differentiation","volume":"97","author":"Pasca di Magliano","year":"2000","journal-title":"Proc Natl Acad Sci."},{"key":"2021122204032692300_CIT0011","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/1471-2164-13-147","article-title":"Genome-wide analysis of Pax8 binding provides new insights into thyroid functions","volume":"13","author":"Ruiz-Llorente","year":"2012","journal-title":"BMC Genomics."},{"issue":"1","key":"2021122204032692300_CIT0012","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."},{"issue":"1","key":"2021122204032692300_CIT0013","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 (Oxf)."},{"issue":"7","key":"2021122204032692300_CIT0014","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 vitro studies reveal different pathogenic mechanisms","volume":"23","author":"Hermanns","year":"2013","journal-title":"Thyroid."},{"issue":"6","key":"2021122204032692300_CIT0015","doi-asserted-by":"crossref","first-page":"E977","DOI":"10.1210\/jc.2010-2341","article-title":"Mutations in the NKX2.5 gene and the PAX8 promoter in a girl with thyroid dysgenesis","volume":"96","author":"Hermanns","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122204032692300_CIT0016","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1210\/jcem.86.8.7765","article-title":"A novel 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 Clin Endocrinol Metab."},{"issue":"9","key":"2021122204032692300_CIT0017","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 Clin Endocrinol Metab."},{"issue":"1","key":"2021122204032692300_CIT0018","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 Clin Endocrinol Metab."},{"issue":"11","key":"2021122204032692300_CIT0019","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 Clin Endocrinol Metab."},{"issue":"7","key":"2021122204032692300_CIT0020","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."},{"issue":"5-6","key":"2021122204032692300_CIT0021","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.mcp.2008.06.003","article-title":"Identification and characterization of new variants of three associated SNPs and a microsatellite in the TSH receptor gene which are useful for genetic studies","volume":"22","author":"Esperante","year":"2008","journal-title":"Mol Cell Probes."},{"issue":"4","key":"2021122204032692300_CIT0022","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":"2021122204032692300_CIT0023","doi-asserted-by":"crossref","first-page":"619013","DOI":"10.4061\/2010\/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 Thyroid Res."},{"key":"2021122204032692300_CIT0024","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13039-014-0085-4","article-title":"A de novo 10.79 Mb interstitial deletion at 2q13q14.2 involving PAX8 causing hypothyroidism and mullerian agenesis: a novel case report and literature review","volume":"7","author":"Ma","year":"2014","journal-title":"Mol Cytogenet."},{"issue":"5","key":"2021122204032692300_CIT0025","doi-asserted-by":"crossref","first-page":"8707","DOI":"10.18632\/oncotarget.14419","article-title":"Identification and characterization of novel PAX8 mutations in congenital hypothyroidism(CH) in a Chinese population","volume":"8","author":"Liu","year":"2017","journal-title":"Oncotarget."},{"issue":"9","key":"2021122204032692300_CIT0026","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1089\/thy.2012.0649","article-title":"A new 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."},{"issue":"2","key":"2021122204032692300_CIT0027","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."},{"issue":"1-2","key":"2021122204032692300_CIT0028","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."},{"issue":"5","key":"2021122204032692300_CIT0029","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."},{"issue":"6","key":"2021122204032692300_CIT0030","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1157\/13123286","article-title":"Estudio transversal espa\u00f1ol de crecimiento 2008. Parte I: valores de peso y longitud en reci\u00e9n nacidos de 26-42 semanas de edad gestacional. Spanish cross-sectional growth study 2008. Part I: weight and height values in newborns of 26-42 weeks of gestational age","volume":"68","author":"Carrascosa Lezcano","year":"2008","journal-title":"An Pediatr."},{"issue":"11","key":"2021122204032692300_CIT0031","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1097\/CM9.0000000000000213","article-title":"Novel non-synonymous mutations of PAX8 in a cohort of Chinese with congenital hypothyroidism","volume":"132","author":"Qian","year":"2019","journal-title":"Chin Med J (Engl)."},{"issue":"16","key":"2021122204032692300_CIT0032","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"2021122204032692300_CIT0033","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"issue":"6","key":"2021122204032692300_CIT0034","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS recommendations for the description of sequence variants: 2016 update","volume":"37","author":"den Dunnen","year":"2016","journal-title":"Hum Mutat."},{"issue":"W1","key":"2021122204032692300_CIT0035","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI search and sequence analysis tools APIs in 2019","volume":"47","author":"Madeira","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"2021122204032692300_CIT0036","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/j.1432-1033.1995.tb20338.x","article-title":"Distinct functional properties of three human paired-box-protein, PAX8, isoforms generated by alternative splicing in thyroid, kidney and Wilms\u2019 tumors","volume":"228","author":"Poleev","year":"1995","journal-title":"Eur J Biochem."},{"issue":"3","key":"2021122204032692300_CIT0037","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."},{"issue":"5","key":"2021122204032692300_CIT0038","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."},{"issue":"6","key":"2021122204032692300_CIT0039","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 (Oxf)."},{"issue":"7-8","key":"2021122204032692300_CIT0040","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 Pediatr Endocrinol Metab."},{"issue":"9","key":"2021122204032692300_CIT0041","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":"L\u00f6f","year":"2016","journal-title":"Thyroid."},{"issue":"2","key":"2021122204032692300_CIT0042","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 Pediatr Endocrinol Metab."},{"issue":"4","key":"2021122204032692300_CIT0043","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 Clin Endocrinol Metab."},{"issue":"2","key":"2021122204032692300_CIT0044","doi-asserted-by":"crossref","first-page":"E333","DOI":"10.1210\/jc.2014-2605","article-title":"Exome sequencing for the diagnosis of 46,XY disorders of sex development","volume":"100","author":"Baxter","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122204032692300_CIT0045","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1172\/JCI118123","article-title":"Congenital human thyroglobulin defect due to low expression of the thyroid-specific transcription factor TTF-1","volume":"96","author":"Acebr\u00f3n","year":"1995","journal-title":"J Clin Invest."},{"key":"2021122204032692300_CIT0046","doi-asserted-by":"crossref","first-page":"619013","DOI":"10.4061\/2010\/619013","article-title":"Case report congenital hypothyroidism caused by a PAX8 gene mutation manifested as sodium\/iodide symporter gene defect","volume":"2010","author":"Jo","year":"2010","journal-title":"J Thyroid Res."},{"issue":"1","key":"2021122204032692300_CIT0047","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1089\/thy.2008.0116","article-title":"Clinical and molecular analysis of thyroid hypoplasia: a population-based approach in southern Brazil","volume":"19","author":"Ramos","year":"2009","journal-title":"Thyroid."},{"issue":"5","key":"2021122204032692300_CIT0048","doi-asserted-by":"crossref","first-page":"e010719","DOI":"10.1136\/bmjopen-2015-010719","article-title":"Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism","volume":"6","author":"Fu","year":"2016","journal-title":"BMJ Open."},{"issue":"3","key":"2021122204032692300_CIT0049","first-page":"1061","article-title":"Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping","volume":"84","author":"Pannain","year":"1999","journal-title":"J Clin Endocrinol Metab."},{"key":"2021122204032692300_CIT0050","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."},{"issue":"1","key":"2021122204032692300_CIT0051","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1530\/acta.0.1040027","article-title":"Concentration of plasma thyroglobulin and urinary excretion of iodinated material in the diagnosis of thyroid disorders in congenital hypothyroidism","volume":"104","author":"Gons","year":"1983","journal-title":"Acta Endocrinol (Copenh)."},{"issue":"1","key":"2021122204032692300_CIT0052","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1089\/thy.1993.3.37","article-title":"Spectrum of serum thyroglobulin elevation in congenital thyroid disorders","volume":"3","author":"Heinze","year":"1993","journal-title":"Thyroid."},{"issue":"6","key":"2021122204032692300_CIT0053","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1530\/EJE-17-1017","article-title":"The genetic characteristics of congenital hypothyroidism in China by comprehensive screening of 21 candidate genes","volume":"178","author":"Sun","year":"2018","journal-title":"Eur J Endocrinol."},{"key":"2021122204032692300_CIT0054","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0079-6603(00)66033-6","article-title":"A unique combination of transcription factors controls differentiation of thyroid cells","volume":"66","author":"Damante","year":"2001","journal-title":"Prog Nucleic Acid Res Mol Biol."},{"issue":"9","key":"2021122204032692300_CIT0055","first-page":"4230","article-title":"Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid-specific promoters","volume":"12","author":"Zannini","year":"1992","journal-title":"Mol Cell Biol."},{"issue":"5","key":"2021122204032692300_CIT0056","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.1074\/jbc.M205977200","article-title":"The paired domain-containing factor Pax8 and the homeodomain-containing factor TTF-1 directly interact and synergistically activate transcription","volume":"278","author":"Di Palma","year":"2003","journal-title":"J Biol Chem."},{"issue":"4","key":"2021122204032692300_CIT0057","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 Pediatr."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa711\/33851124\/dgaa711.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/1\/e152\/41847427\/dgaa711.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/1\/e152\/41847427\/dgaa711.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T04:10:08Z","timestamp":1640146208000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/1\/e152\/5919357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":57,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,10,8]]},"published-print":{"date-parts":[[2021,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa711","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2020,10,8]]}}}