title: Absence of cell-surface EpCAM in congenital tufting enteropathy.
abstract: Mutations in the epithelial cell adhesion molecule (EpCAM; CD326) gene are causal for congenital tufting enteropathy (CTE), a disease characterized by intestinal abnormalities resulting in lethal diarrhea in newborns. Why the different mutations all lead to the same disease is not clear. Here, we report that most mutations, including a novel intronic variant, will result in lack of EpCAM's transmembrane domain, whereas two mutations allow transmembrane localization. We find that these mutants are not routed to the plasma membrane, and that truncated mutants are secreted or degraded. Thus, all epcam mutations lead to loss of cell-surface EpCAM, resulting in CTE.
authors: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Ulrike
authors: U
authors: Schnell
authors: Jeroen
authors: J
authors: Kuipers
authors: James L
authors: JL
authors: Mueller
authors: Anneke
authors: A
authors: Veenstra-Algra
authors: Mamata
authors: M
authors: Sivagnanam
authors: Ben N G
authors: BN
authors: Giepmans
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003967:Diarrhea / Q000235:genetics* / Q000378:metabolism*; D000071858:Epithelial Cell Adhesion Molecule; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D021381:Protein Transport; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule