title: Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease.
abstract: Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Two susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene. Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association. Here, we report heterozygous EDNRB missense mutations (G57S, R319W and P383L) in isolated HSCR. These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features. In addition, the present data give further support to the role of the endothelin-signalling pathway in the development of neural crest-derived enteric neurons.
authors.affiliation: Service de Génétique Médicale and Clinique Chirurgicale Infantile, Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: D
authors.initials: D
authors.lastname: Jan
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: P
authors.initials: P
authors.lastname: Edery
authors.forename: C
authors.initials: C
authors.lastname: Bidaud
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: P
authors.initials: P
authors.lastname: Tam
authors.forename: J
authors.initials: J
authors.lastname: Simeoni
authors.forename: E
authors.initials: E
authors.lastname: Flori
authors.forename: C
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
mesh_terms: D005260:Female; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin