Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome.
Exp Clin Endocrinol Diabetes
; 126(2): 85-90, 2018 02.
Article
en En
| MEDLINE
| ID: mdl-28954305
ABSTRACT
OBJECTIVE:
To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome. DESIGN, PATIENTS, MEASUREMENTS We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-binding capability and the transcriptional activity of the two mutated transcription factors were investigated in vitro.RESULTS:
The NKX2.1 mutation did not show any transcriptional activity and had almost no DNA-binding. The PAX8 mutation was normally located to the nucleus and showed a normal transactivation and a normal binding to the known downstream targets.CONCLUSIONS:
The molecular defect explaining the phenotype of brain-lung-thyroid syndrome was identified. To what extent the PAX8 mutation contributes to the phenotype needs to be further investigated. We recommend to screen patients with CH and TD for mutations in all known TD candidate genes.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Dificultad Respiratoria del Recién Nacido
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Atetosis
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Corea
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Hipotiroidismo Congénito
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Factor de Transcripción PAX8
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Factor Nuclear Tiroideo 1
Tipo de estudio:
Prognostic_studies
Límite:
Child
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Humans
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Male
Idioma:
En
Revista:
Exp Clin Endocrinol Diabetes
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania