title: New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease.
abstract: OBJECTIVE
  Hirschsprung disease is characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses within distal intestine, because of a fail in the enteric nervous system formations process. Endothelin-3-endothelin receptor B signaling pathway is known to play an essential role in this process. The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum.
  
  
  METHODS
  We performed the mutational screening of both genes in 196 patients with Hirschsprung disease using denaturing high-performance liquid chromatography technology. A case-control study using TaqMan Technology was also carried out to evaluate some common polymorphisms and haplotypes as susceptibility factors for Hirschsprung disease.
  
  
  RESULTS
  Besides several novel mutations in both genes, we found a truncating mutation in an alternative isoform of EDNRB. Interestingly, we obtained an overrepresentation of a specific EDN3 haplotype in cases versus controls.
  
  
  CONCLUSIONS
  Our results suggest that the isoform EDNRB Delta 3 might be playing an essential role in the formation of enteric nervous system. In addition, based on the haplotype distribution, EDN3 might be considered as a common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion.
authors.affiliation: Unidad de Gestión Clínica de Genética, Reproducción y Medicina Fetal, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Avencia
authors.initials: A
authors.lastname: Sánchez-Mejías
authors.forename: Raquel Maria
authors.initials: RM
authors.lastname: Fernández
authors.forename: Manuel
authors.initials: M
authors.lastname: López-Alonso
authors.forename: Guillermo
authors.initials: G
authors.lastname: Antiñolo
authors.forename: Salud
authors.initials: S
authors.lastname: Borrego
mesh_terms: D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004314:Down Syndrome / Q000150:complications / Q000235:genetics; D019334:Endothelin-3 / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D044023:Receptor, Endothelin B / Q000235:genetics*; D012016:Reference Values; D017384:Sequence Deletion
chemical_list: D019334:Endothelin-3; D044023:Receptor, Endothelin B