Glial cell line-derived neurotrophic factor differentially stimulates ret mutants associated with the multiple endocrine neoplasia type 2 syndromes and Hirschsprung's disease.
To investigate the contribution of GDNF to the phenotype observed in this kindred, we scanned the coding region of GDNF in the patient with MEN2/HSCR, but no mutation was found.
GDNF expression was studied immunohistochemically in surgical specimens from 30 HD cases (27 classic forms and 3 ultralong forms) and from 10 age-matched controls.
Recent studies have shown that mutations in endothelin-B receptor (EDNRB), endothelin-3, RET, glial cell line-derived neurotrophic factor (GDNF) genes are responsible for the occurrence of congenital aganglionosis.
GDNF sequence variants including R93W have been suggested previously to represent low penetrance susceptibility mutations for Hirschsprung disease and the R93W was not identified in 376 control alleles studied by others.
As Gdnf and Ret have been linked to the development of Hirschsprung disease (HSCR), it seems likely that Gfra1 could also be a susceptibility gene for HSCR.