EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift


The epithelial cell adhesion molecule gene (EPCAM, previously known as TACSTD1 or TROP1) encodes a membrane-bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3′ end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556-14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype–phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.


  • Sagar J. Pathak
  • James L. Mueller
  • Kevin Okamoto
  • Barun Das
  • Jozef Hertecant
  • Lynn Greenhalgh
  • Trevor Cole
  • Vered Pinsk
  • Baruch Yerushalmi
  • Odul E. Gurkan
  • Michael Yourshaw
  • Erick Hernandez
  • Sandy Oesterreicher
  • Sandhia Naik
  • Ian R. Sanderson
  • Irene Axelsson
  • C. Richard Boland
  • Martin G. Martin
  • Christopher D. Putnam
  • Mamata Sivagnanam
Enheter & grupper
Externa organisationer
  • University of California, San Diego
  • Birmingham Women’s Hospital Healthcare NHS Trust
  • University of California, Los Angeles
  • Miami Jewish Health Systems
  • Queen Mary University
  • Skåne University Hospital
  • Tawam University Hospital
  • Liverpool Women's NHS Foundation Trust
  • Ben Gurion University of the Negev
  • Gazi University
  • Rocky Mountain Pediatric Gastroenterology

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik


Sidor (från-till)142-161
TidskriftHuman Mutation
Tidigt onlinedatum2018 nov 21
StatusPublished - 2019 feb
Peer review utfördJa