JOURNAL ARTICLE

New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease

Avencia Sánchez-Mejías, Raquel Maria Fernández, Manuel López-Alonso, Guillermo Antiñolo, Salud Borrego
Genetics in Medicine: Official Journal of the American College of Medical Genetics 2010, 12 (1): 39-43
20009762

PURPOSE: Hirschsprung disease is characterized by the absence of intramural ganglion cells in the myenteric and submucosal plexuses within distal intestine, because of a fail in the enteric nervous system formations process. Endothelin-3-endothelin receptor B signaling pathway is known to play an essential role in this process. The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum.

METHODS: We performed the mutational screening of both genes in 196 patients with Hirschsprung disease using denaturing high-performance liquid chromatography technology. A case-control study using TaqMan Technology was also carried out to evaluate some common polymorphisms and haplotypes as susceptibility factors for Hirschsprung disease.

RESULTS: Besides several novel mutations in both genes, we found a truncating mutation in an alternative isoform of EDNRB. Interestingly, we obtained an overrepresentation of a specific EDN3 haplotype in cases versus controls.

CONCLUSIONS: Our results suggest that the isoform EDNRB Delta 3 might be playing an essential role in the formation of enteric nervous system. In addition, based on the haplotype distribution, EDN3 might be considered as a common susceptibility gene for sporadic Hirschsprung disease in a low-penetrance fashion.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
20009762
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.