Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene.
J Clin Endocrinol Metab
; 94(1): 197-203, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18957494
ABSTRACT
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(-/-) 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. 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. PARTICIPANT This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3,460 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 <15) and total T(4) 245 nmol/liter (N = 120-350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day.RESULTS:
Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient's 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.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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
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6_ODS3_enfermedades_notrasmisibles
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7_ODS3_muertes_prevenibles_nacidos_ninos
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Respiratória
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Fatores de Transcrição
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Proteínas Nucleares
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Hipotireoidismo
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Mutação
Limite:
Animals
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Female
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Humans
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Newborn
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2009
Tipo de documento:
Article