Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation
- 1 August 1995
- journal article
- case report
- Published by Wiley in Annals of Neurology
- Vol. 38 (2), 163-169
- https://doi.org/10.1002/ana.410380207
Abstract
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.Keywords
This publication has 15 references indexed in Scilit:
- Mitochondria1 encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNA Leu(UUR) geneNeurology, 1995
- A T → C mutation at nt 8993 of mitochondrial DNA in a child with Leigh syndromeNeurology, 1994
- A second missense mutation in the mitochondrial ATPase 6 gene in Leigh's syndromeAnnals of Neurology, 1993
- Electron transfer complex I defect in idiopathic dystoniaAnnals of Neurology, 1992
- Subacute necrotizing encephalopathyNeurology, 1992
- Mitochondrial oxidative phosphorylation defects in parkinson's diseaseAnnals of Neurology, 1991
- Alternative, simultaneous complex I mitochondrial DNA mutations in Leber's hereditary optic neuropathyBiochemical and Biophysical Research Communications, 1991
- Evaluation of procedures for assaying oxidative phosphorylation enzyme activities in mitochondrial myopathy muscle biopsiesBiochimica et Biophysica Acta (BBA) - Bioenergetics, 1990
- Familial mitochondrial encephalomyopathy (MERRF): Genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA diseaseCell, 1988
- Purification of three iron-sulfur proteins from the iron-protein fragment of mitochondrial NADH-ubiquinone oxidoreductaseBiochemistry, 1982