Idiopathic slow-transit constipation is not associated with mutations of the RET proto-oncogene or GDNF

PURPOSE: Idiopathic slow-transit constipation is a severe disorder of unkno wn cause. The onset in early childhood and history of constipation or Hirsc hsprung's disease in close family relatives suggest that slow-transit const ipation could have a genetic basis. Several germline mutations have been de scribed in Hirschsprung's disease, including mutations of RET and the gene encoding its ligand glial cell-derived neurotrophic factor. The aim of this study was to screen a panel of 16 cases of familial idiopathic slow-transi t constipation, including 4 families in which there were relatives with Hir schsprung's disease, for RET and glial cell-derived neurotrophic factor mut ations previously identified in Hirschsprung's disease. METHODS: Genomic DN A from 16 patients with slow-transit constipation and four relatives with H irschsprung's disease was analyzed using single strand and heteroduplex con formation polymorphism analysis at two conditions and by direct DNA sequenc ing using the fluorescent dideoxy terminator method. RESULTS: Although comm on sequence polymorphisms were demonstrated with a frequency comparable wit h published data, no published or new mutation was seen in any of the exons of RET or glial cell-derived neurotrophic factor. CONCLUSIONS: Mutation of RET or glial cell-derived neurotrophic factor is not a frequent cause of i diopathic slow-transit constipation.