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

Autor: Pathak SJ; Department of Pediatrics, University of California, San Diego, La Jolla, California.; Rady Children's Hospital, San Diego, California., Mueller JL; Department of Pediatrics, University of California, San Diego, La Jolla, California., Okamoto K; Department of Pediatrics, University of California, San Diego, La Jolla, California., Das B; Department of Pediatrics, University of California, San Diego, La Jolla, California., Hertecant J; Genetics/Metabolics Service, Tawam Hospital, Al Ain, United Arab Emirates., Greenhalgh L; Liverpool Women's NHS Foundation Trust, Liverpool, UK., Cole T; West Midlands Regional Genetics Service and Birmingham Health Partners, Birmingham Women's Hospital, Birmingham, UK., Pinsk V; Division of Pediatrics, Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Yerushalmi B; Division of Pediatrics, Pediatric Gastroenterology Unit, Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Gurkan OE; Department of Pediatrics, Gazi University School of Medicine, Ankara, Turkey., Yourshaw M; Department of Human Genetics, University of California, Los Angeles, Los Angeles, California., Hernandez E; Pediatric Gastroenterology, Miami Children's Health System, Miami, Florida., Oesterreicher S; Rocky Mountain Health Pediatric Gastroenterology, Lone Tree, Colorado., Naik S; Paediatric Gastroenterology, Barts and the London School of Medicine, London, UK., Sanderson IR; Paediatric Gastroenterology, Barts and the London School of Medicine, London, UK., Axelsson I; Department of Pediatrics, Skane University Hospital, Malmo, Sweden., Agardh D; Department of Clinical Sciences, Lund University, Skane University Hospital, Malmo, Sweden., Boland CR; Department of Medicine, University of California, San Diego, La Jolla, California., Martin MG; Department of Pediatrics, University of California, Los Angeles, Los Angeles, California., Putnam CD; Department of Medicine, University of California, San Diego, La Jolla, California.; San Diego Branch, Ludwig Institute for Cancer Research, La Jolla, California., Sivagnanam M; Department of Pediatrics, University of California, San Diego, La Jolla, California.; Rady Children's Hospital, San Diego, California.
Jazyk: angličtina
Zdroj: Human mutation [Hum Mutat] 2019 Feb; Vol. 40 (2), pp. 142-161. Date of Electronic Publication: 2018 Nov 29.
DOI: 10.1002/humu.23688
Abstrakt: 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.
(© 2018 The Authors. Human Mutation published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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