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Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms

Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure with electrolyte imbalances and impaired growth. CTE is typically diagnosed by its characteristic histological features, including villous atrophy, crypt hyperplasia and focal epit...

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Autores principales: Das, Barun, Sivagnanam, Mamata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793535/
https://www.ncbi.nlm.nih.gov/pubmed/33374714
http://dx.doi.org/10.3390/jcm10010019
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author Das, Barun
Sivagnanam, Mamata
author_facet Das, Barun
Sivagnanam, Mamata
author_sort Das, Barun
collection PubMed
description Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure with electrolyte imbalances and impaired growth. CTE is typically diagnosed by its characteristic histological features, including villous atrophy, crypt hyperplasia and focal epithelial tufts consisting of densely packed enterocytes. Mutations in the EPCAM and SPINT2 genes have been identified as the etiology for this disease. The significant morbidity and mortality and lack of direct treatments for CTE patients demand a better understanding of disease pathophysiology. Here, the latest knowledge of CTE biology is systematically reviewed, including clinical aspects, disease genetics, and research model systems. Particular focus is paid to the pathogenesis of CTE and predicted mechanisms of the disease as these would provide insight for future therapeutic options. The contribution of intestinal homeostasis, including the role of intestinal cell differentiation, defective enterocytes, disrupted barrier and cell–cell junction, and cell-matrix adhesion, is vividly described here (see Graphical Abstract). Moreover, based on the known dynamics of EpCAM signaling, potential mechanistic pathways are highlighted that may contribute to the pathogenesis of CTE due to either loss of EpCAM function or EpCAM mutation. Although not fully elucidated, these pathways provide an improved understanding of this devastating disease.
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spelling pubmed-77935352021-01-09 Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms Das, Barun Sivagnanam, Mamata J Clin Med Review Congenital tufting enteropathy (CTE) is an autosomal recessive disease of infancy that causes severe intestinal failure with electrolyte imbalances and impaired growth. CTE is typically diagnosed by its characteristic histological features, including villous atrophy, crypt hyperplasia and focal epithelial tufts consisting of densely packed enterocytes. Mutations in the EPCAM and SPINT2 genes have been identified as the etiology for this disease. The significant morbidity and mortality and lack of direct treatments for CTE patients demand a better understanding of disease pathophysiology. Here, the latest knowledge of CTE biology is systematically reviewed, including clinical aspects, disease genetics, and research model systems. Particular focus is paid to the pathogenesis of CTE and predicted mechanisms of the disease as these would provide insight for future therapeutic options. The contribution of intestinal homeostasis, including the role of intestinal cell differentiation, defective enterocytes, disrupted barrier and cell–cell junction, and cell-matrix adhesion, is vividly described here (see Graphical Abstract). Moreover, based on the known dynamics of EpCAM signaling, potential mechanistic pathways are highlighted that may contribute to the pathogenesis of CTE due to either loss of EpCAM function or EpCAM mutation. Although not fully elucidated, these pathways provide an improved understanding of this devastating disease. MDPI 2020-12-23 /pmc/articles/PMC7793535/ /pubmed/33374714 http://dx.doi.org/10.3390/jcm10010019 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Das, Barun
Sivagnanam, Mamata
Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title_full Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title_fullStr Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title_full_unstemmed Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title_short Congenital Tufting Enteropathy: Biology, Pathogenesis and Mechanisms
title_sort congenital tufting enteropathy: biology, pathogenesis and mechanisms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793535/
https://www.ncbi.nlm.nih.gov/pubmed/33374714
http://dx.doi.org/10.3390/jcm10010019
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