Dataset Information

New mutation in EPCAM for congenital tufting enteropathy: A case report.

ABSTRACT:

Background

Congenital tufting enteropathy (CTE) is a rare cause of diarrhea in children. However, it can result in early-onset of chronic diarrhea and failure to thrive. Children with this disease have to depend on total parenteral nutrition (TPN), and eventually small intestine transplantation. The epithelial cell adhesion molecule (EPCAM) gene was identified to be associated with CTE. Here, we present a case of an infant with CTE due to a mutation not reported in the literature before.

Case summary

A 1-year and 7-mo infant boy exhibited intractable watery diarrhea and mushy stool within 1 wk after birth, for which he had required medical treatment and hospitalization several times. His sister presented similar symptoms and died at the age of two. On admission, his body weight was 5700 g (-4.8SDS) and measured 66 cm (-5.4SDS) in height. Meanwhile, he cannot speak or climb. He exhibited mild anemia, hypocalcemia, hypomagnesemia, and an infection in the upper respiratory tract. Microvilli sparse and vacuolar degeneration of epithelial cells were reported by small intestine biopsy. Whole-exome sequencing showed a novel homozygous splice mutation (c.657+1[IVS6] G>A) in the EPCAM gene. He was treated with TPN and recombinant human growth hormone. After 2 mo, his body weight was up to 8500 g and he has been waiting for small bowel transplantation.

Conclusion

CTE is rare but fatal. Patients with CTE require rapid diagnosis and therapy to improve their survival.

SUBMITTER: Zhou YQ

PROVIDER: S-EPMC7642537 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New mutation in <i>EPCAM</i> for congenital tufting enteropathy: A case report.

Zhou Yan-Qiong YQ Wu Guo-Sheng GS Kong Yuan-Mei YM Zhang Xiao-Yuan XY Wang Chun-Lin CL

World journal of clinical cases 20201001 20

<h4>Background</h4>Congenital tufting enteropathy (CTE) is a rare cause of diarrhea in children. However, it can result in early-onset of chronic diarrhea and failure to thrive. Children with this disease have to depend on total parenteral nutrition (TPN), and eventually small intestine transplantation. The epithelial cell adhesion molecule (<i>EPCAM)</i> gene was identified to be associated with CTE. Here, we present a case of an infant with CTE due to a mutation not reported in the literature ...[more]

PMID: 33195669

Similar Datasets

Project description:Congenital tufting enteropathy (CTE) is an autosomal recessive disease characterized by severe intestinal failure in infancy and mutations in the epithelial cell adhesion molecule (EPCAM) gene. Previous studies of CTE in mice expressing mutant EpCAM show neonatal lethality. Hence, to study the cellular, molecular, and physiological alterations that result from EpCAM mutation, a tamoxifen-inducible mutant EpCAM enteroid model has been generated. The presence of mutant EpCAM in the model was confirmed at both mRNA and protein levels. Immunofluorescence microscopy demonstrated the reduced expression of mutant EpCAM. Mutant enteroids had reduced budding potential as well as significantly decreased mRNA expression for epithelial lineage markers (Mucin 2, lysozyme, sucrase-isomaltase), proliferation marker Ki67, and secretory pathway transcription factors (Atoh1, Hnf1b). Significantly decreased numbers of Paneth and goblet cells were confirmed by staining. These findings were correlated with intestinal tissue from CTE patients and the mutant mice model that had significantly fewer Paneth and goblet cells than in healthy counterparts. FITC-dextran studies demonstrated significantly impaired barrier function in monolayers derived from mutant enteroids compared with control monolayers. In conclusion, we have established an ex vivo CTE model. The role of EpCAM in the budding potential, differentiation, and barrier function of enteroids is noted. Our study establishes new facets of EpCAM biology that will aid in understanding the pathophysiology of CTE and role of EpCAM in health and disease.NEW & NOTEWORTHY Here, we develop a novel ex vivo enteroid model for congenital tufting enteropathy (CTE) based on epithelial cell adhesion molecule (EPCAM) gene mutations found in patients. With this model we demonstrate the role of EpCAM in maintaining the functional homeostasis of the intestinal epithelium, including differentiation, proliferation, and barrier integrity. This study further establishes a new direction in EpCAM biology that will help in understanding the detailed pathophysiology of CTE and role of EpCAM.