Mutation in 5′ Upstream Region of GCHI Gene Causes Familial Dopa-Responsive Dystonia

The document reports on a study that identified a mutation in the 5' upstream region of the GCHI gene, which is associated with familial dopa-responsive dystonia (DRD). The study involved a family of Irish/French-Canadian ethnicity spanning three generations, with ten family members undergoing neurological exams and providing blood samples. Six subjects had dystonia, all experiencing onset in a foot or leg during childhood, with varying disease durations and symptom spread. The mutation -22C>T in the GCHI gene was found to segregate with the affected status in the family and was not present in 53 control samples or in 214 clinical samples from the Massachusetts General Hospital Neurogenetics DNA Diagnostic Laboratory. This suggests that the -22C>T mutation is pathogenic and results in DRD. The affected subjects showed a good response to therapeutic doses of carbidopa/levodopa or ropinirole, confirming the diagnosis of DRD.