Levodopa-responsive dystonia - GTP cyclohydrolase I or parkin mutations?

Autosomal dominant DOPA-responsive dystonia (DRD) is usually caused by muta tion in the gene encoding guanosine triphosphate-cyclohydrolase I (GTPCH I) . We studied 22 families with a phenotype of levodopa-responsive dystonia b y sequencing the six coding exons, the 5'-untranslated region and the exon- intron boundaries of the GTPCH I gene, Eleven heterozygous mutations were i dentified, including five missense mutations, one splice site mutation, two small deletions and two nonsense mutations, in 12 families that included 2 7 patients and 13 asymptomatic carriers, Six mutations were new and five ha d already been reported, Four of the mutations caused truncation of the GTP CH I protein, One family carried a base-pair change in the 5'-untranslated region, not detected in controls, that could be responsible for the phenoty pe, Three of the remaining 10 families had deletions in the parkin gene on chromosome 6, underlining how difficult it is to distinguish, in some cases , between DRD and parkin mutations, No mutations were identified in seven f amilies, The clinical spectrum extended from the classical DRD phenotype to parkinsonism with levodopa-induced dyskinesias, and included spastic parap legia as well as the absence of dystonia.