Is there a role for the IHH gene in Hirschsprung's disease?

Neurogastroenterol Motil. 2003 Dec;15(6):663-8. doi: 10.1046/j.1350-1925.2003.00447.x.


Hirschsprung disease (HSCR) is characterized by the absence of ganglion cells along a variable length of the intestine. HSCR has a complex genetic aetiology with 50% of the patients unexplained by mutations in the major HSCR genes. The Ihh gene is involved in the development of the enteric nervous system (ENS) and Ihh mutant mice present with a phenotype reminiscent of HSCR. The requirement of Ihh signalling for the proper development of the ENS, together with the evidence presented by the Ihh murine model, prompted us to investigate the involvement of the human IHH gene in HSCR. Sequence analysis revealed seven single nucleotide polymorphisms, six of which were new. Allele and haplotype frequencies were compared between cases and controls, and, among the cases, between genders, between different phenotypes, and between patients with different mutation status in the main HSCR genes. Despite the involvement of IHH in the development of the ENS, IHH is not a major gene in HSCR. Nevertheless, as the manifestation of the HSCR phenotype is genetic background dependent, polymorphic loci should be tested simultaneously to characterize gene-gene interaction. The involvement of IHH in other intestinal anomalies should be investigated.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chi-Square Distribution
  • Female
  • Gene Frequency / genetics
  • Hedgehog Proteins
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Polymorphism, Genetic / genetics*
  • Sequence Analysis, DNA / methods
  • Trans-Activators / genetics*
  • Trans-Activators / physiology


  • Hedgehog Proteins
  • Trans-Activators