Identification of EpCAM as the Gene for Congenital Tufting Enteropathy

Abstract

Correspondence: Mamata Sivagnanam, Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California San Diego, 9500 Gilman Drive, MC 0669, La Jolla, CA 92093, USA, mengineer@ucsd.edu, phone 619-543-7544, fax 619-543-7537. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflicts of Interest: None NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptBackground and Aims-Congenital Tufting Enteropathy (CTE) is a rare autosomal recessive diarrheal disorder presenting in the neonatal period. CTE is characterized by intestinal epithelial cell dysplasia leading to severe malabsorption and significant morbidity and mortality. The pathogenesis and genetics of this disorder are not well understood. The objective of this study was to identify the gene responsible for CTE.

Cleavage and Cell Adhesion Properties of Human Epithelial Cell Adhesion Molecule (HEPCAM)

“…In the first published knock-out report, deletion of mEpcam resulted in embryonic lethality at day 12.5 of gestation due to placental defects in the differentiation or survival of parietal giant trophoblast cells (6). Later, Guerra et al (7) and Lei et al (8) independently published a perinatally lethal phenotype of mEpcam knock-out mice, due to severe intestinal problems, resembling a human lethal disorder termed congenital tufting enteropathy, which is associated with mutations of the epcam gene (9). Although Lei et al (8) reported a certain degree of embryonic lethality, the reasons for these obvious discrepancies in phenotypes remain unknown.…”

Tufting Enteropathy with EpCAM Mutations in Two Siblings

“…2 Recently, mutations in the epithelial cell adhesion molecule (EpCAM) gene have been identified as responsible for tufting enteropathy. 11 We report two Korean siblings with tufting enteropathy confirmed by genetic analysis.…”

Matriptase-mediated cleavage of EpCAM destabilizes claudins and dysregulates intestinal epithelial homeostasis

“…Truncating and selected missense mutations in EPCAM (encoding epithelial cell adhesion molecule [EpCAM; CD326]) cause a severe autosomal recessive childhood diarrheal syndrome termed congenital tufting enteropathy (CTE) (1,2). CTE is characterized by widespread small intestinal epithelial dysplasia, and intestinal mucosal biopsies demonstrate distinctive "tufts" of epithelial cells at the tips of blunted villi (1,3).…”

“…CTE is characterized by widespread small intestinal epithelial dysplasia, and intestinal mucosal biopsies demonstrate distinctive "tufts" of epithelial cells at the tips of blunted villi (1,3). EpCAM is a cell surface glycoprotein that is present in many developing epithelia, some adult epithelia (including intestine), carcinomas, tumor-initiating cells, circulating tumor cells, and tissue and embryonic stem cells (4,5).…”