{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:26:43Z","timestamp":1787963203284,"version":"build-2784847793"},"reference-count":38,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Brain\u2013lung\u2013thyroid syndrome (BLTS) is caused by\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      haploinsufficiency, resulting in chorea\/choreoathetosis, respiratory problems, and hypothyroidism. Genes interacting with NKX2-1 mutants influence its phenotypic variability. We report a novel\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      missense variant and the modifier function of TAZ\/WWTR1 in BLTS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      A child with BLTS underwent next-generation sequencing panel testing for thyroid disorders. His family was genotyped for\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      variants and screened for germline mosaicism. Mutant\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      was generated, and transactivation assays were performed on three NKX2-1 target gene promoters. DNA binding capacity and protein\u2013protein interaction were analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The patient had severe BLTS and carried a novel missense variant c.632A&gt;G (p.N211S) in\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      , which failed to bind to specific DNA promoters, reducing their transactivation.\n                      <jats:italic toggle=\"yes\">TAZ<\/jats:italic>\n                      cotransfection did not significantly increase transcription of these genes, although the variant retained its ability to bind to TAZ.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      We identify a novel pathogenic\n                      <jats:italic toggle=\"yes\">NKX2-1<\/jats:italic>\n                      variant that causes severe BLTS and is inherited through germline mosaicism. The mutant lacks DNA-binding capacity, impairing transactivation and suggesting that NKX2-1 binding to DNA is essential for TAZ-mediated transcriptional rescue.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2023.0593","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T07:11:20Z","timestamp":1715929880000},"page":"942-948","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Missense Variant in the NKX2-1\n                    <i>Homeodomain<\/i>\n                    Prevents Transcriptional Rescue by TAZ"],"prefix":"10.1177","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4498-561X","authenticated-orcid":false,"given":"Beatriz","family":"Villafuerte","sequence":"first","affiliation":[{"name":"Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Carrasco-L\u00f3pez","sequence":"additional","affiliation":[{"name":"\u201cSols-Morreale\u201d Biomedical Research Institute, Higher Council for Scientific Research (CSIC), Autonomous University of Madrid, Ciberonc, Carlos III Health Institute (ISCIII), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3385-9378","authenticated-orcid":false,"given":"Amanda","family":"Herranz","sequence":"additional","affiliation":[{"name":"Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Garz\u00f3n","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Pediatrics Department, 12 de Octubre University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogelio","family":"Sim\u00f3n","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Pediatrics Department, 12 de Octubre University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Natera-de-Benito","sequence":"additional","affiliation":[{"name":"Neuromuscular Diseases Unit, Pediatric Neurology, Sant Joan de D\u00e9u Hospital, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pouya","family":"Alikhani","sequence":"additional","affiliation":[{"name":"Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jair","family":"Tenorio","sequence":"additional","affiliation":[{"name":"Institute for Medical and Molecular Genetics (INGEMM), IdiPAZ, Center for Biomedical Research on the Rare Diseases Network (CIBERER), Carlos III Health Institute (ISCIII), ITHACA-European Reference Network, La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fe","family":"Garc\u00eda-Santiago","sequence":"additional","affiliation":[{"name":"Cytogenetics Section, Institute for Medical and Molecular Genetics (INGEMM), Center for Biomedical Research on the Rare Diseases Network (CIBERER), Carlos III Health Institute (ISCIII), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Solis","sequence":"additional","affiliation":[{"name":"Bioinformatics Section, Institute for Medical and Molecular Genetics (INGEMM), IdiPAZ, Center for Biomedical Research on the Rare Diseases Network (CIBERER), Carlos III Health Institute (ISCIII), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngela","family":"del-Pozo","sequence":"additional","affiliation":[{"name":"Bioinformatics Section, Institute for Medical and Molecular Genetics (INGEMM), IdiPAZ, Center for Biomedical Research on the Rare Diseases Network (CIBERER), Carlos III Health Institute (ISCIII), La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"Institute for Medical and Molecular Genetics (INGEMM), IdiPAZ, Center for Biomedical Research on the Rare Diseases Network (CIBERER), Carlos III Health Institute (ISCIII), ITHACA-European Reference Network, La Paz University Hospital, Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Dar\u00edo","family":"Ortigoza-Escobar","sequence":"additional","affiliation":[{"name":"Movement Disorders Unit, Pediatric Neurology, Sant Joan de D\u00e9u Hospital, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Santisteban","sequence":"additional","affiliation":[{"name":"\u201cSols-Morreale\u201d Biomedical Research Institute, Higher Council for Scientific Research (CSIC), Autonomous University of Madrid, Ciberonc, Carlos III Health Institute (ISCIII), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-5308","authenticated-orcid":false,"given":"Jos\u00e9 C.","family":"Moreno","sequence":"additional","affiliation":[{"name":"Thyroid Molecular Laboratory, Institute for Medical and Molecular Genetics (INGEMM), La Paz University Hospital Research Institute (IdiPAZ), La Paz University Hospital, Madrid, Spain."},{"name":"Unit 735, Center for Biomedical Research on the Rare 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