title: A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf.
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).
authors.affiliation: Département de Génétique, Université Paris Descartes, Unité INSERM U781, Hôpital Necker-Enfants Malades, 75015 Paris, France. julie.salomon@nck.aphp.fr
authors.forename: Julie
authors.initials: J
authors.lastname: Salomon
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Espinosa-Parrilla
authors.forename: Olivier
authors.initials: O
authors.lastname: Goulet
authors.forename: Wafa'a
authors.initials: W
authors.lastname: Al-Qabandi
authors.forename: Philippe
authors.initials: P
authors.lastname: Guigue
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.forename: Julie
authors.initials: J
authors.lastname: Bruneau
authors.forename: Fatema
authors.initials: F
authors.lastname: Alzahrani
authors.forename: Saleh
authors.initials: S
authors.lastname: Almuhsen
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Marc
authors.initials: M
authors.lastname: Jeanpierre
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D003241:Consanguinity; D004252:DNA Mutational Analysis; D000071858:Epithelial Cell Adhesion Molecule; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D007410:Intestinal Diseases / Q000151:congenital / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D007730:Kuwait; D008297:Male; D009154:Mutation; D010375:Pedigree; D011780:Qatar
chemical_list: D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule