{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:30:16Z","timestamp":1790847016397,"version":"4.1.0"},"reference-count":29,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Context: Thyroid transcription factor 1 (TITF1\/NKX2.1) is expressed in the thyroid, lung, ventral forebrain, and pituitary. In the lung, TITF1\/NKX2.1 activates the expression of genes critical for lung development and function. Titf\/Nkx2.1\u2212\/\u2212 mice have pituitary and thyroid aplasia but also impairment of pulmonary branching. Humans with heterozygous TITF1\/NKX2.1 mutations present with various combinations of primary hypothyroidism, respiratory distress, and neurological disorders.<\/jats:p>\n               <jats:p>Objective: The objective of the study was to report clinical and molecular studies of the first patient with lethal neonatal respiratory distress from a novel heterozygous TITF1\/NKX2.1 mutation.<\/jats:p>\n               <jats:p>Participant: This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3460 g and Apgar scores were normal. Soon after birth, she developed acute respiratory failure with pulmonary hypertension. At neonatal screening on the second day of life, TSH was 31 mU\/liter (N &amp;lt;15) and total T4 245 nmol\/liter (N = 120\u2013350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day.<\/jats:p>\n               <jats:p>Results: Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient\u2019s lymphocyte DNA revealed a novel heterozygous TITF1\/NKX2.1 mutation (I207F). This mutation was not found in either parent. In vitro, the mutant TITF-1 had reduced DNA binding and transactivation capacity.<\/jats:p>\n               <jats:p>Conclusion: This is the first reported case of a heterozygous TITF1\/NKX2.1 mutation leading to neonatal death from respiratory failure. The association of severe unexplained respiratory distress in a term neonate with mild primary hypothyroidism is the clue that led to the diagnosis.<\/jats:p>","DOI":"10.1210\/jc.2008-1402","type":"journal-article","created":{"date-parts":[[2008,10,29]],"date-time":"2008-10-29T02:13:39Z","timestamp":1225246419000},"page":"197-203","source":"Crossref","is-referenced-by-count":66,"title":["Lethal Respiratory Failure and Mild Primary Hypothyroidism in a Term Girl with a de Novo Heterozygous Mutation in the TITF1\/NKX2.1 Gene"],"prefix":"10.1210","volume":"94","author":[{"given":"Emilie","family":"Maquet","sequence":"first","affiliation":[{"name":"IRIBHM and Genetics Service (E.M., S.C., J.P., C.C.-H., G.V.), Erasme Hospital, Free University of Brussels ULB, B-1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Costagliola","sequence":"first","affiliation":[{"name":"IRIBHM and Genetics Service (E.M., S.C., J.P., C.C.-H., G.V.), Erasme 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