title: Mutation of the endothelin-3 gene in the Waardenburg-Hirschsprung disease (Shah-Waardenburg syndrome).
abstract: Hirschsprung disease (HSCR) and Waardenburg sundrome (WS) are congenital malformations regarded as neurocristopathies since both disorders involve neural crest-derived cells. The WS-HSCR association (Shah-Waardenburg syndrome) is a rare autosomal recessive condition that occasionally has been ascribed to mutations of the endothelin-receptor B (EDNRB) gene. WS-HSCR mimicks the megacolon and white coat-spotting observed in Ednrb mouse mutants. Since mouse mutants for the EDNRB ligand, endothelin-3 (EDN3), displayed a similar phenotype, the EDN3 gene was regarded as an alternative candidate gene in WS-HSCR. Here, we report a homozygous substitution/deletion mutation of the EDN3 gene in a WS-HSCR patient. EDN3 thus becomes the third known gene (after RET and EDNRB) predisposing to HSCR, supporting the view that the endothelin-signaling pathways play a major role in the development of neural crests.
authors.affiliation: Service de Génétique Médicale et Unité de Recherches sur les Handicaps Génétiques de l'Enfant, Hôpital des Enfants Malades, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Edery
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: R M
authors.initials: RM
authors.lastname: Hofstra
authors.forename: H
authors.initials: H
authors.lastname: Martelli
authors.forename: C
authors.initials: C
authors.lastname: Bidaud
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D016232:Endothelins / Q000235:genetics* / Q000502:physiology; D005260:Female; D005808:Genes, Recessive; D006627:Hirschsprung Disease / Q000150:complications* / Q000209:etiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009432:Neural Crest / Q000254:growth & development; D010641:Phenotype; D014849:Waardenburg Syndrome / Q000150:complications* / Q000209:etiology / Q000235:genetics*
chemical_list: D016232:Endothelins; D004247:DNA