{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:56:04Z","timestamp":1779378964532,"version":"3.53.1"},"reference-count":22,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T00:00:00Z","timestamp":1623628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004061","name":"Oesterreichische Nationalbank","doi-asserted-by":"publisher","award":["17968"],"award-info":[{"award-number":["17968"]}],"id":[{"id":"10.13039\/501100004061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Tufting enteropathy (TE) is caused by recessive EPCAM mutations, and is characterized by intractable diarrhea of congenital onset and disorganization of enterocytes. TE generally requires parenteral nutrition (PN) during childhood or intestinal bowel transplantation. We report three unrelated families with six children with TE. We highlight the high rate of disease-related mortality. We observe adequate weight gain with PN, but low to normal and stunted body length, supporting the recent notion that a short stature might be intrinsic to TE. The diagnosis of TE in the index patients from each family was delayed for months to years, even when clinical data, duodenal biopsies, or exome sequencing data were obtained early on. We identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A &gt; G (p.Gln109Arg), and nonsense mutation c.429G &gt; A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A &gt; G (Tyr186Phefs*6). Homozygosity for p.Gln109Arg was associated with absent EPCAM staining, and compound heterozygosity for p.Trp143*\/Tyr186Phefs*6 was associated with reduced EPCAM staining in duodenal biopsies; such observations might contribute to a genotype\u2013phenotype correlation in larger cohorts of TE patients. This study extends the clinical and molecular spectrum of TE.<\/jats:p>","DOI":"10.3390\/children8060503","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T22:25:46Z","timestamp":1623709546000},"page":"503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Three Novel EPCAM Variants Causing Tufting Enteropathy in Three Families"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5604-9722","authenticated-orcid":false,"given":"Hasret","family":"Ayy\u0131ld\u0131z Civan","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology, Hepatology and Nutrititon, Health Science University, Istanbul Bak\u0131rkoy Dr. Sadi Konuk Education and Research Hospital, 34147 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coleen","family":"Leitner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"\u00d6streicher","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Klinikum Neukoelln, 12351 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Maria","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Cremer","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Klinikum Neukoelln, 12351 Berlin, Germany"},{"name":"Department of Neonatology, Charit\u00e9 University Medical Center, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6970-336X","authenticated-orcid":false,"given":"Johannes A.","family":"Mayr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Klinikum Neukoelln, 12351 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8908-5589","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7155-0315","authenticated-orcid":false,"given":"Andreas R.","family":"Janecke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics I, Medical University of Innsbruck, 6020 Innsbruck, Austria"},{"name":"Division of Human Genetics, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/j.1536-4801.1994.tb11192.x","article-title":"Tufting enteropathy: A newly recognized clinicopathological entity associated with refractory diarrhea in infants","volume":"18","author":"Reifen","year":"1994","journal-title":"J. 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