A gene for Hirschsprung disease (megacolon) in the pericentromeric region of human chromosome 10

Nat Genet. 1993 Aug;4(4):351-6. doi: 10.1038/ng0893-351.


Hirschsprung disease (HSCR) is characterized by a congenital absence of enteric ganglia along a variable length of the intestine. Although long considered to be a multifactorial disease, we have identified linkage in a subset of five HSCR families to the pericentromeric region of chromosome 10, thereby providing monogenic inheritance in some families. A maximum two-point lod score of 3.37 (theta = 0.045) was observed between HSCR and D10S176, under an incompletely penetrant dominant model. Multipoint, affecteds-only and non-parametric analyses supported this finding and localize this gene to a region of approximately 7 centiMorgans, in close proximity to the locus for multiple endocrine neoplasia type 2 (MEN2). The co-occurrence of these two entities in some families might be attributable to shared pathogenetic origins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Centromere*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 10*
  • Family
  • Female
  • Genetic Linkage
  • Genetic Markers
  • Genotype
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Pedigree


  • Genetic Markers