Familial dystonia and visual failure with striatal CT lucencies.

Marsden, C. D.; Lang, Anthony E.; Quinn, Niall; McDonald, W. I.; Abdallat, A; Nimri, Sarah M. Al

doi:10.1136/jnnp.49.5.500

Cited by 46 publications

(12 citation statements)

References 41 publications

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“…23 Other families with hereditary optic atrophy, dystonia, and striatal CT lucencies have been reported. 24 A few recent case studies describe dystonia in isolated individuals with biochemically identified abnormalities of mitochondrial metabolism. 25,26 Mitochondrial complex I abnormalities have been identified in a number of individuals with sporadic as well as familial dystonia.…”

Section: Discussionmentioning

confidence: 99%

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation

et al. 1999

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A variety of neurologic phenotypes have been described in patients with mitochondrial disorders. We report a 32‐year‐old man in whom dystonia was the salient and presenting feature of a mitochondrial DNA mutation. He presented at age 23 with writer's cramp and progressed over 5 years to exhibit dystonia in facial muscles and lower limbs. He also has exercise intolerance, mild, bilateral ptosis, proximal muscle weakness, and sensorineural hearing loss. Molecular genetic analysis of blood, urine, and muscle biopsy demonstrated the presence of a heteroplasmic point mutation at nucleotide position 3243. The 3243 mtDNA mutation has pleomorphic manifestations, and dystonia should be added to the list of associated clinical features.

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Section: Discussionmentioning

confidence: 99%

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation

et al. 1999

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“…The seemingly specific association of LHON, movement disorders, and a complex I biochemical defect observed for both the ND6 np 14459 mutation and the ND6 np 14484 plus ND1 np 4160 mutations raises the possibility that optic nerve and basal ganglion neurons are acutely sensitive to the pathogenic effects of complex I defects. Possibly, additional ND6 mutations also contribute to the etiology of LHON and/or dystonia with basal ganglion lucencies (4,9,10,34).…”

Section: Discussionmentioning

confidence: 99%

Use of Transmitochondrial Cybrids To Assign a Complex I Defect to the Mitochondrial DNA-Encoded NADH Dehydrogenase Subunit 6 Gene Mutation at Nucleotide Pair 14459 That Causes Leber Hereditary Optic Neuropathy and Dystonia

Jun

Trounce

Brown

et al. 1996

Molecular and Cellular Biology

140

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A heteroplasmic G-to-A transition at nucleotide pair (np) 14459 within the mitochondrial DNA (mtDNA)-encoded NADH dehydrogenase subunit 6 (ND6) gene has been identified as the cause of Leber hereditary optic neuropathy (LHON) and/or pediatric-onset dystonia in three unrelated families. This ND6 np 14459 mutation changes a moderately conserved alanine to a valine at amino acid position 72 of the ND6 protein. Enzymologic analysis of mitochondrial NADH dehydrogenase (complex I) with submitochondrial particles isolated from Epstein-Barr virus-transformed lymphoblasts revealed a 60% reduction (P < 0.005) of complex I-specific activity in patient cell lines compared with controls, with no differences in enzymatic activity for complexes II plus III, III, and IV. This biochemical defect was assigned to the ND6 np 14459 mutation by using transmitochondrial cybrids in which patient Epstein-Barr virus-transformed lymphoblast cell lines were enucleated and the cytoplasts were fused to a mtDNA-deficient ( 0 ) lymphoblastoid recipient cell line. Cybrids harboring the np 14459 mutation exhibited a 39% reduction (P < 0.02) in complex I-specific activity relative to wild-type cybrid lines but normal activity for the other complexes. Kinetic analysis of the np 14459 mutant complex I revealed that the V max of the enzyme was reduced while the K m remained the same as that of wild type. Furthermore, specific activity was inhibited by increasing concentrations of the reduced coenzyme Q analog decylubiquinol. These observations suggest that the np 14459 mutation may alter the coenzyme Q-binding site of complex I.

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“…44 A Leber's-like optic neuropathy has been associated with dystonia and basal gangliar lesions in several pedigrees. [45][46][47][48][49][50] Leigh-like encephalopathy, periaqueductal syndrome and other brainstem involvement have also rarely been reported. [51][52][53] Disease clinically indistinguishable from multiple sclerosis may occur in families with LHON.…”

Section: Leber's Hereditary Optic Neuropathymentioning

confidence: 99%

Hereditary optic neuropathies

Newman

Biousse

2004

Eye

151

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Aims To provide a clinical update on the hereditary optic neuropathies. Methods Review of the literature. Results The hereditary optic neuropathies comprise a group of disorders in which the cause of optic nerve dysfunction appears to be hereditable, based on familial expression or genetic analysis. In some hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. In others, various neurologic and systemic abnormalities are regularly observed. Conclusion The most common hereditary optic neuropathies are autosomal dominant optic atrophy (Kjer's disease) and maternally inherited Leber's hereditary optic neuropathy. We review the clinical phenotypes of these and other inherited disorders with optic nerve involvement.

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Familial dystonia and visual failure with striatal CT lucencies.

Cited by 46 publications

References 41 publications

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation

Use of Transmitochondrial Cybrids To Assign a Complex I Defect to the Mitochondrial DNA-Encoded NADH Dehydrogenase Subunit 6 Gene Mutation at Nucleotide Pair 14459 That Causes Leber Hereditary Optic Neuropathy and Dystonia

Hereditary optic neuropathies

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