The contributions of RET noncoding variation to Hirschsprung disease

Zachary E. Stine, Andrew S. McCallion

Research output: Chapter in Book/Report/Conference proceedingChapter


First described by Danish pediatrician Harald Hirschsprung, Hirschsprung disease (HSCR) is a disorder of the enteric nervous system characterized by the absence of variable length of the submucous (Meissner's) and myenteric (Auerbach's) plexuses in the distal gut. As a defect in neural crest-derived cell population, Hirschsprung disease is considered a neurocristopathy. While HSCR was originally observed in sporadic cases, the advent of lifesaving surgical intervention has also given rise to the observation of familial forms of HSCR. Subsequently, its presentation in familial, sporadic, and syndromic form illuminated the genetics of HSCR. As this work has progressed the ret proto-oncogene (RET), a receptor tyrosine kinase has emerged as a central player in the development of HSCR, most frequently modified in effect by the contributions of risk alleles at other loci. This has been exemplified by the recent characterization of risk variants in a noncoding RET regulatory element, establishing it as a model for the study of multigenic disorders.

Original languageEnglish (US)
Title of host publicationGene Regulatory Sequences and Human Disease
PublisherSpringer New York
Number of pages26
ISBN (Electronic)9781461416838
ISBN (Print)1461416825, 9781461416821
StatePublished - Sep 1 2011


  • Cis-regulatory element
  • Disease
  • Enhancer
  • Enteric nervous system
  • Hirschsprung
  • NRG1
  • Neural crest
  • RET
  • SOX10
  • Transcriptional regulation

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)


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