BACKGROUND: Enteric aganglionosis in Hirschsprung disease has been linked to 
genes coding for endothelin-3 (EDN3) and the endothelin B receptor (EDNRB), but 
there is no such linkage in most patients with sporadic Hirschsprung disease. 
However, the similarity between the distal colonic aganglionosis in Hirschsprung 
disease and that due to EDN3 or EDNRB mutations led to the hypothesis that 
levels of expression of these genes might be affected in the absence of 
mutation, thus causing the Hirschsprung disease phenotype. The aim of this study 
was to determine EDN3 and EDNRB messenger RNA (mRNA) levels in tissue samples 
from patients with sporadic Hirschsprung disease.
METHODS: RNA and DNA were isolated from the ganglionic and aganglionic colonic 
segments of ten children with sporadic Hirschsprung disease, and from the colon 
of ten age-matched controls. The DNA was analysed for mutations in the genes 
coding for endothelin-3 (ET-3) and endothelin B receptor (ET-B) proteins. 
Relative levels of EDN3 and EDNRB mRNA were determined by semi-quantitative 
transcriptase-polymerase chain reaction.
RESULTS: Three children had sequence variants in EDN3 and EDNRB. In the 
remaining seven patients, EDN3 mRNA levels were reduced in both the ganglionic 
and aganglionic colon compared with levels in controls; there was no difference 
in expression of EDNRB between groups.
CONCLUSION: In the absence of mutation, EDN3 is downregulated in short-segment 
Hirschsprung disease, suggesting that this may be a common step leading to 
aganglionosis.