BACKGROUND: Hirschsprung disease (HSCR) is a congenital disorder characterized 
by an absence of ganglion cells in the nerve plexuses of the lower digestive 
tract. HSCR has a complex pattern of inheritance and is sometimes associated 
with mutations in genes of the receptor tyrosine kinase (RET) and endothelin 
receptor B (EDNRB) signaling pathways, which are crucial for development of the 
enteric nervous system.
METHODS: Using PCR amplification and direct sequencing, we screened for 
mutations and polymorphisms in the coding regions and intron/exon boundaries of 
the RET, GDNF, EDNRB, and EDN3 genes of 84 HSCR patients and 96 ethnically 
matched controls.
RESULTS: We identified 10 novel and 2 previously described mutations in RET, and 
4 and 2 novel mutations in EDNRB and in EDN3, respectively. Potential 
disease-causing mutations were detected in 24% of the patients. The overall 
mutation rate was 41% in females and 19% in males (P = 0.06). RET mutations 
occurred in 19% of the patients. R114H in RET was the most prevalent mutation, 
representing 7% of the patients or 37% of the patients with RET mutations. To 
date, such a high frequency of a single mutation has never been reported in 
unrelated HSCR patients. Mutations in EDNRB, EDN3, and GDNF were found in four, 
two, and none of the patients, respectively. Two patients with mutations in 
genes of the EDNRB pathway also harbored a mutation in RET. Three novel and 
three reported polymorphisms were found in EDNRB, EDN3, and GDNF.
CONCLUSION: This study identifies additional HSCR disease-causing mutations, 
some peculiar to the Chinese population, and represents the first comprehensive 
genetic analysis of sporadic HSCR disease in Chinese.