{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:10:35Z","timestamp":1787008235332,"version":"build-2736575974"},"reference-count":27,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"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":[[2014,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Homozygous loss-of-function mutations in the\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      gene have been reported in several patients with partial or complete Bamforth\u2013Lazarus syndrome: congenital hypothyroidism (CH) with thyroid dysgenesis (usually athyreosis), cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. Here, our objective was to evaluate potential functional consequences of a\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      mutation in a patient with a similar clinical phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      was sequenced in eight patients with thyroid dysgenesis and cleft palate. Transient transfection was performed in HEK293 cells using the thyroglobulin (TG) and thyroid peroxidase (TPO) promoters in luciferase reporter plasmids to assess the functional impact of the\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      mutations. Primary human thyrocytes transfected with wild type and mutant\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      served to assess the impact of the mutation on endogenous TG and TPO expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We identified and characterized the function of a new homozygous\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      missense mutation (p.R73S) in a boy with a typical phenotype (athyreosis, cleft palate, and partial choanal atresia). This new mutation located within the forkhead domain was inherited from the heterozygous healthy consanguineous parents.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      functional studies in HEK293 cells showed that this mutant gene enhanced the activity of the\n                      <jats:italic toggle=\"yes\">TG<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TPO<\/jats:italic>\n                      gene promoters (1.5-fold and 1.7-fold respectively vs. wild type\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      ;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt;0.05), unlike the five mutations previously reported in Bamforth\u2013Lazarus syndrome. The gain-of-function effect of the\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      -p.R73S mutant gene was confirmed by an increase in endogenous TG production in primary human thyrocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>\n                      We identified a new homozygous\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      mutation responsible for enhanced expression of the\n                      <jats:italic toggle=\"yes\">TG<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TPO<\/jats:italic>\n                      genes in a boy whose phenotype is similar to that reported previously in patients with loss-of-function\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      mutations. This finding further delineates the role for\n                      <jats:italic toggle=\"yes\">FOXE1<\/jats:italic>\n                      in both thyroid and palate development, and shows that enhanced gene activity should be considered among the mechanisms underlying Bamforth\u2013Lazarus syndrome.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2013.0417","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T05:03:58Z","timestamp":1384319038000},"page":"649-654","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["A Novel\n                    <i>FOXE1<\/i>\n                    Mutation (R73S) in Bamforth\u2013Lazarus Syndrome Causing Increased Thyroidal Gene Expression"],"prefix":"10.1177","volume":"24","author":[{"given":"Aurore","family":"Carr\u00e9","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]},{"name":"Universit\u00e9 Paris-Sud","place":["France"]},{"name":"H\u00f4pital Necker\u2014Enfants Malades","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasha T.","family":"Hamza","sequence":"additional","affiliation":[{"name":"Ain Shams University","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dulanjalee","family":"Kariyawasam","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc","family":"Guillot","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Pierre-et-Marie-Curie","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapha\u00ebl","family":"Teissier","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Tron","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Castanet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]},{"name":"H\u00f4pital Charles Nicolle,","place":["France"]},{"name":"H\u00f4pital Necker\u2014Enfants Malades","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Dupuy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Sud","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El Kholy","sequence":"additional","affiliation":[{"name":"Ain Shams University","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Polak","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Descartes","place":["France"]},{"name":"H\u00f4pital Necker\u2014Enfants Malades","place":["France"]},{"name":"H\u00f4pital Necker\u2014Enfants Malades","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,4,1]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3040981"},{"key":"e_1_3_3_3_2","first-page":"1297","article-title":"Identification of a cis-regulatory element and a thyroid-specific nuclear factor mediating the hormonal regulation of rat thyroid peroxidase promoter activity","volume":"7","author":"Aza-Blanc P","year":"1993","unstructured":"Aza-Blanc P, , Di Lauro R, , Santisteban P. 1993. 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