Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation

John M. Shoffner, Michael D. Brown, Carol Stugard, Albert S. June, Stephen Pollock, Richard H. Haas, Allan Kaufman, Deborah Koontz, Yoon Kim, Jennifer R. Graham, Edwin Smith, John Dixon, Douglas C. Wallace

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


A Novemberel 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 pedigress. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The dAugusthter 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 herediatary 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.

Original languageEnglish (US)
Pages (from-to)163-169
Number of pages7
JournalAnnals of neurology
Issue number2
StatePublished - Aug 1995
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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