A novel point mutation in the ND6 subunit of complex I at position 14,459 of the 
mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for 
the highly tissue-specific disease. Leber's hereditary optic neuropathy plus 
dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, 
other pedigrees with the mutation are needed to confirm its association with the 
disease. Clinical, biochemical, and genetic characterization is reported in two 
additional pedigrees. Leber's hereditary optic neuropathy developed in two 
family members in one pedigree. The daughter had clinically silent basal ganglia 
lesions. In a second pedigree, a single individual presented with 
childhood-onset generalized dystonia and bilateral basal ganglia lesions. 
Patient groups that included individuals with Leigh's disease, dystonia plus 
complex neurodegeneration, and Leber's hereditary optic neuropathy did not 
harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a 
high degree of tissue specificity, thus producing a narrow phenotypic range. 
These results confirm the association of the MTND6*LDYT14459A mutation with 
Leber's hereditary optic neuropathy and/or dystonia. As the first genetic 
abnormality that has been identified to cause generalized dystonia, this 
mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative 
phosphorylation genes are important considerations in the pathogenesis of 
dystonia.