MITOCHONDRIAL-DNA IN FOCAL DYSTONIA - A CYBRID ANALYSIS

The cause and pathophysiology of dystonia remain unknown. The recent i dentification of mitochondrial complex I deficiency in platelets from patients with sporadic focal dystonia suggests that a defect of energy metabolism may be relevant in a proportion of patients. We have addre ssed the possible contribution of mitochondrial DNA (mtDNA) to the com plex I deficiency in dystonia by the use of genome transfer technology . platelets from patients deficient for complex I were fused with A549 rho(0) (mtDNA-less) cells to form cybrids comprising the A549 nucleus and dystonia mtDNA. Mixed cybrid cell lines were analyzed for 9 contr ols and 9 dystonia patients, and clonal cybrid lines were generated fo r 2 control and 2 dystonia patients. Subsequent biochemical analysis s howed that the dystonia complex I defect was complemented in both the mixed and the clonal cybrid lines. These results contrast with similar studies in mitochondrial myopathy and Parkinson's disease patients, i n which the mitochondrial defect was maintained in at least a proporti on of A549 cybrids, and suggest that the complex I defect in dystonia is not caused by an mtDNA mutation.