Hirschsprung's disease, also known as: congenital aganglionic megacolon, is caused by an aganglionic section of bowel (the normal enteric nerves are absent) that starts at the anus and progresses upwards.
Symptoms:enlargement of the colon, caused by bowel obstruction.
There are two basic forms: familial, and, sporadic. The RET gene is implicated in both, but to varying degrees, and in all cases, there appear to be as yet unknown additional genes (or influences) that can modify the risk associated with any given RET variant.
In the familial form of Hirschsprung disease, RET gene coding sequence mutations can be found in ~50% of all patients, whereas for the sporadic form, generally less than a third of patients have an identifiable RET gene coding mutation.[PMID 11953745]
A RET variant occuring within an intron has also been found (rs2435357), and in conjunction with other evidence, has led to the notion that most probably all Hirschsprung disease patients have some mutation in their RET gene, and such variants are necessary but not sufficient to actually exhibit the disease. Mutations at additional loci are presumably also required.[PMID 15829955]
Note that this complex and most likely additive mode of inheritance makes it particularly tricky to assess risk based only on the status of single SNP, or even the subset of all SNPs that may happen to be represented on a given microarray.
The following are SNPs in the RET gene that represent identified Hirschsprung disease associated mutations:
SNPs in other genes associated with Hirschsprung disease include: