title: Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease.
abstract: Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Four susceptibility genes have recently been identified in HSCR, namely the RET proto-oncogene, the glial cell line-derived neurotrophic factor (GDNF), the endothelin B receptor (EDNRB) and the endothelin-3 genes (EDN3). Homozygosity for EDN3 mutations has been previously shown to cause the Shah-Waardenburg syndrome, a combination of HSCR with features of the Waardenburg syndrome. Here, we report on heterozygous EDN3 missense mutations in isolatec HSCR. 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 the possibility that either recessive or weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation.
authors.affiliation: INSERM U-393, Département de Gńétique, and Clinique Chirurgicale Infantile, Hôpital des Enfants-Malades, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Bidaud
authors.forename: R
authors.initials: R
authors.lastname: Salomon
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: T
authors.initials: T
authors.lastname: Attié
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: M
authors.initials: M
authors.lastname: Bonduelle
authors.forename: J
authors.initials: J
authors.lastname: Amiel
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*; D005091:Exons; D005260:Female; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D013577:Syndrome; D014849:Waardenburg Syndrome / Q000235:genetics
chemical_list: D019334:Endothelin-3; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas