title: Novel Mutations in EPCAM Cause Congenital Tufting Enteropathy.
abstract: OBJECTIVE
  Congenital tufting enteropathy (CTE) is a rare autosomal recessive form of intractable diarrhea of infancy. Patients develop chronic diarrhea within days after birth, leading to severe malabsorption and significant mortality. CTE is characterized by subtotal villous atrophy with crypt hyperplasia. Typical features include abnormal villi in the intestinal epithelium and disorganization of surface enterocytes with focal crowding, resembling tufts. The pathogenesis of CTE remains poorly understood. CTE has been reported in Western populations, but until now had not been reported in China. The objective of this study was to identify the gene responsible for CTE in a Chinese individual.
  
  
  METHODS
  A 13-year-old girl with suspected CTE, whose parents were both healthy, was evaluated in our clinic. Tissues were obtained by endoscopy and examined by electron microscopy. Genomic DNA, extracted from the peripheral blood of the child and parents, was subjected to whole-exome sequencing. After mutations in the gene encoding epithelial cell adhesion molecule (EPCAM) were identified, expression of EPCAM was examined by immunohistochemistry staining.
  
  
  RESULTS
  Whole-exome sequencing revealed compound heterozygous mutations in EPCAM in the patient, with immunohistochemical analysis showing complete loss of EPCAM expression in the intestinal villi and crypts.
  
  
  CONCLUSIONS
  We identified compound heterozygous mutations in EPCAM, with loss of EPCAM expression in duodenal enterocytes, in a patient with intractable diarrhea since infancy who was subsequently diagnosed with CTE. This is the first case of CTE to be reported in a Chinese patient.
authors.affiliation: Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Tang
authors.affiliation: Divisions of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Taosheng
authors.initials: T
authors.lastname: Huang
authors.affiliation: Sinopath Diagnostics, Beijing, China.
authors.forename: Zhongyao
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002681:China; D003937:Diagnosis, Differential; D003968:Diarrhea, Infantile / Q000175:diagnosis / Q000235:genetics*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008286:Malabsorption Syndromes / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation
chemical_list: D000071858:Epithelial Cell Adhesion Molecule