R Gath, A Goessling, et al, Analysis of the RET, GDNF, EDN3
, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease, Gut: 2001, 48:671-675.
No mutations were found in the GDNF, EDNRB and EDN3 genes (data not shown).
The GDNF, ENDRB, and EDN3 genes also affect the penetrance of RET mutations (4,5,14).
Analysis of the RET, GDNF, EDNRB and EDN3 genes in Chinese Hirschsprung's patients.
The primers and PCR conditions for amplification of the RET and EDN3 genes have been described previously (6,12).
We analyzed the coding regions of the RET, GDNF, EDNRB, and EDN3 genes in 84 Chinese patients with sporadic HSCR.
We found two novel mutations in the EDN3 gene: a missense mutation (E48D) in exon 2 resulting from a G>C transversion; and a de novo C>A transversion at nucleotide -19 from the start codon (5'UT -19C>A), which could be affecting as yet unexplored regulatory regions.
Mutations in EDNRB and EDN3 were scarce and were mainly inherited from unaffected parents.
Whether E48D in EDN3 and N426N in EDNRB, contribute to the phenotype in combination with the mutations in RET is not known, but this certainly adds force to the interaction between pathways (18-21).
4] Nonstandard abbreviations: HSCR, Hirschsprung disease; SSA, short-segment aganglionosis; LSA, long-segment aganglionosis; ENS, enteric nervous system; RET, receptor tyrosine kinase; EDNRB, endothelin receptor B; GDNF, glial cell-line-derived neurotrophic factor; EDN3, endothelin 3; TCA, total colonic aganglionosis; CCHS, congenital central hypoventilation syndrome; CD, cadherin domain; TK, tyrosine kinase; and SNP, single-nucleotide polymorphism.