Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation
| Autor: | Donald R. Johns, James P. Sutton, M. F. Beal, S. E. Browne, Stefan M. Pulst, David Simon |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Genetics Mutation Mitochondrial DNA Genome Base Sequence Point mutation Parkinsonism Leber's hereditary optic neuropathy Brain Middle Aged Biology medicine.disease medicine.disease_cause DNA Mitochondrial Heteroplasmy Pedigree Parkinsonian Disorders medicine Humans Point Mutation Missense mutation Female Neurology (clinical) Gene |
| Zdroj: | Neurology. 53:1787-1787 |
| ISSN: | 1526-632X 0028-3878 |
| DOI: | 10.1212/wnl.53.8.1787 |
| Popis: | Objective: To investigate a family with maternally inherited, adult-onset multisystem degeneration including prominent parkinsonism to determine whether clinical features can result from a mitochondrial DNA (mtDNA) mutation. The parkinsonism was levodopa responsive and was associated with the loss of pigmented neurons in the substantia nigra in at least one patient. Background: Mitochondrial dysfunction is hypothesized to play a role in late-onset neurodegenerative diseases including PD and AD. Mitochondrial genetic mutations are hypothesized to account for these defects, but attempts to identify specific mtDNA mutations have been inconclusive. Methods: Clinical examinations, DNA sequencing, and restriction digestion and biochemical analyses were performed. Results: Maternal relatives harbor a G-to-A missense mutation, heteroplasmic in some patients, at nucleotide position 11778 of the mitochondrial ND4 gene of complex I that converts a highly conserved arginine to a histidine. Sequencing of the entire mitochondrial genome in an affected family member reveals no other mutations likely to be pathogenic. This mutation has been identified previously only in families with Leber’s hereditary optic neuropathy—a disorder also linked to complex I dysfunction but usually limited clinically to optic atrophy. Conclusions: These data reveal previously unsuspected clinical heterogeneity of the G11778A mutation, and suggest that an inherited mtDNA mutation can contribute to the development of adult-onset parkinsonism and multisystem degeneration. |
| Databáze: | OpenAIRE |
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