Novel mutations of the endothelin-B receptor gene in isolated patients with Hirschsprung's disease

Hum Mol Genet. 1996 Mar;5(3):347-9. doi: 10.1093/hmg/5.3.347.


Hirschsprung's disease (HSCR) is characterized by the absence of autonomic ganglion cells in the terminal bowel and is a relatively common cause of intestinal obstruction in the newborn. The incidence of HSCR is estimated to be 1 in 5000 live births. Recently, the endothelin-B receptor (EDNRB) gene has been shown as a susceptibility gene for HSCR by the production of aganglionic colon in mice with a null mutation of this gene and by demonstrating a missense mutation in a large inbred kindred with a high incidence of HSCR (Mennonite pedigree). However, no further mutations have been demonstrated in other clinical cases. We analysed alterations of the EDNRB gene in 41 isolated patients of HSCR. Two novel mutations were detected: a G to A transition at nucleotide 824 and an insertion of T at nucleotide 878. Both mutations resulted in stop codons, predicted to produce a truncated and non-functional endothelin-B receptor. These observations indicate that dysfunction or loss of function of endothelin-B receptor may be involved in the aetiology of some isolated patients with HSCR.

MeSH terms

  • Codon
  • Exons
  • Hirschsprung Disease / genetics*
  • Humans
  • Mutation*
  • Polymorphism, Single-Stranded Conformational
  • Receptor, Endothelin B
  • Receptors, Endothelin / genetics*


  • Codon
  • Receptor, Endothelin B
  • Receptors, Endothelin