A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf

Eur J Med Genet. 2011 May-Jun;54(3):319-22. doi: 10.1016/j.ejmg.2011.01.009. Epub 2011 Feb 26.

Abstract

Mutations of the EPCAM gene have been recently identified in Congenital Tufting Enteropathy (CTE), a severe autosomal recessive gastrointestinal insufficiency of childhood requiring parenteral nutrition and occasionally intestinal transplantation. Studying seven multiplex consanguineous families from the Arabic peninsula (Kuwait and Qatar) we found that most patients were homozygote for a c.498insC mutation in exon 5. The others carried a novel mutation IVS4-2A→G. Both mutations were predicted to truncate the C-terminal domain necessary to anchorage of EPCAM at the intercellular membrane. Consistently, immunohistochemistry of intestinal biopsies failed to detect the EPCAM protein at the intercellular membrane level. The c.498insC mutation was found on the background of a minimal common haplotype of 473kb suggesting a very old founder effect (5000-6000 yrs).

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Base Sequence
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Consanguinity
  • DNA Mutational Analysis
  • Epithelial Cell Adhesion Molecule
  • Exons / genetics
  • Family Health
  • Female
  • Founder Effect*
  • Genotype
  • Haplotypes
  • Humans
  • Immunohistochemistry
  • Intestinal Diseases / congenital
  • Intestinal Diseases / genetics*
  • Intestinal Mucosa / metabolism
  • Intestines / pathology
  • Kuwait
  • Male
  • Mutation
  • Pedigree
  • Qatar

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule