RESUMO
BACKGROUND: Autosomal dominant dopa-responsive dystonia is commonly caused by mutations in the guanosine triphosphate cyclohydrolase-1 gene. METHODS: We report a British family that has been followed for more than 20 years in which no mutations were previously identified. RESULTS: Reanalysis of this pedigree detected a duplication of guanosine triphosphate cyclohydrolase-1 exon 2 in affected family members. mRNA analysis showed a mutant transcript with a tandem exon 2 duplication. Four family members developed dopa-responsive dystonia, with onset in their late teens, and subsequently developed restless leg syndrome and migraine. CONCLUSIONS: This is the first report of an intragenic guanosine triphosphate cyclohydrolase-1 duplication in a dopa-responsive dystonia family.
