Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B)

Hum Genet. 1998 Aug;103(2):145-8. doi: 10.1007/s004390050797.

Abstract

Hirschsprung disease is a congenital malformation affecting 1 in 5000 live births. The absence of parasympathetic neuronal ganglia (Meissner, Auerbach) in the hindgut results in poor coordination of peristaltic movement, and a varying degree of constipation. Four different genes have been implicated in the pathogenesis of Hirschsprung disease: the RET tyrosine kinase receptor gene; one of its ligands, the glial cell line-derived neurotrophic factor (GDNF) gene; the endothelin receptor B (EDNRB) gene; and its ligand, endothelin-3 (EDN3). Recently, combinations of mutations in two of these genes (RET and GDNF) have been reported in Hirschsprung patients. We report a family with missense mutations in both the RET gene (R982C) and the EDNRB gene (G57S). In this family, three out of five members have the two mutations, but only one, a boy, has the Hirschsprung disease phenotype. This illustrates the complexity of the molecular background of Hirschsprung disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Restriction Enzymes / metabolism
  • Drosophila Proteins*
  • Female
  • Genetic Variation
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, Endothelin B
  • Receptors, Endothelin / genetics*

Substances

  • Drosophila Proteins
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Proto-Oncogene Proteins
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • DNA Restriction Enzymes