title: [Mutations of the endothelin-3 gene in isolated and syndromic forms of Hirschsprung disease].
abstract: OBJECTIVE
  Hirschsprung's disease is a frequent congenital malformation regarded as a multigenic neurocristopathy. Three susceptibility genes have been identified in Hirschsprung's disease, namely the RET proto-oncogene, the Glial cell line-Derived Neurotrophic Factor and the endothelin B receptor. A total of 174 probands with isolated Hirschsprung's disease (59 familial, 117 sporadic cases), and 4 patients with associated Waardenburg's syndrome and Hirschsprung's disease (1 familial, 3 sporadic cases) were screened for mutations in the coding sequence of the endothelin 3 gene. The coding sequence of the endothelin 3 gene was analyzed for point mutations, using a combination of SSCP analysis and direct DNA sequencing.
  
  
  RESULTS
  Two heterozygous mutations (A17T and A224T) were identified in two patients with isolated Hirschsprung's disease. Two homozygous truncations mutations (E55X and GC262->T) were identified in patients with the Waardenburg's syndrome/Hirschsprung's disease association.
  
  
  CONCLUSIONS
  The present data give further support to the role of the endothelin-signaling pathway in the development of neural crest-derived enteric neurons. They also suggest that either recessive and weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation.
authors.affiliation: Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Département de Génétique, Hôpital des Enfants Malades, Institut Necker, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Bidaud
authors.forename: R
authors.initials: R
authors.lastname: Salomon
authors.forename: P
authors.initials: P
authors.lastname: Edery
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.forename: C
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: P J
authors.initials: PJ
authors.lastname: Willems
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
mesh_terms: D019334:Endothelin-3 / Q000235:genetics*; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007422:Intestines / Q000294:innervation; D009154:Mutation; D009432:Neural Crest; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction / Q000235:genetics
chemical_list: D019334:Endothelin-3; C000715470:MAS1 protein, human; D021382:Protein Sorting Signals; D000090063:Proto-Oncogene Mas
vernacular_title: Mutations du gène de l'endothéline 3 dans des formes isolées et syndromiques de la maladie de Hirschsprung.