Mutant neurogenin-3 in congenital malabsorptive diarrhea.
N Engl J Med
; 355(3): 270-80, 2006 Jul 20.
Article
en En
| MEDLINE
| ID: mdl-16855267
ABSTRACT
BACKGROUND:
Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells.METHODS:
We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays.RESULTS:
The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had normal numbers of Paneth's, goblet, and absorptive cells. We identified two homozygous mutations in NEUROG3, both of which rendered the NEUROG3 protein unable to activate NEUROD1, a downstream target of NEUROG3, and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter. The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression.CONCLUSIONS:
A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mutación Missense
/
Diarrea
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Intestino Delgado
/
Síndromes de Malabsorción
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Humans
/
Male
/
Newborn
Idioma:
En
Revista:
N Engl J Med
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA