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Homoplasmy, heteroplasmy, and mitochondrial dystonia.
- Source :
-
Neurology [Neurology] 2007 Aug 28; Vol. 69 (9), pp. 911-6. - Publication Year :
- 2007
-
Abstract
- Background: In clinical practice, mitochondrial disease is seldom considered until a variable combination of seizures, alteration in tone, muscle weakness, and developmental problems is evident. However, it is not uncommon for one symptom to occur in isolation and dominate the clinical phenotype. We report six patients from two families where dystonia was the principal clinical manifestation. A mitochondrial etiology was considered in each case because of the association of dystonia with other less prominent clinical features such as epilepsy.<br />Methods: Histochemical and biochemical analyses were undertaken in skeletal muscle biopsies from individuals in both families. Sequencing of skeletal muscle mtDNA was also performed and suspected mutations were quantified by hot last cycle PCR-RFLP or primer extension assay. Functional consequences of one of the mutations were investigated by measurement of steady state levels of mitochondrial tRNA.<br />Results: Two distinct mitochondrial pathologies were identified: a novel, homoplasmic mitochondrial tRNA(Cys) (MTTC) mutation and the primary, m.11778G>A Leber hereditary optic neuropathy (LHON) mutation. The mild nature of both mutations has permitted very high levels of mutated mtDNA to accumulate. Patients with the mutation in the MTTC gene have no wild type mtDNA detectable and although the LHON mutation is heteroplasmic in the patients we report, it is commonly observed to be homoplasmic.<br />Conclusions: The mitochondrial etiology identified in these patients emphasizes the pathologic potential of homoplasmic mutations and has important implications for the investigation and genetic counseling of families where dystonia is the principal clinical feature. We advocate that mitochondrial disease should be given serious consideration in patients with familial, progressive dystonia, particularly when additional neurologic features such as epilepsy are present.
- Subjects :
- Adult
Basal Ganglia pathology
Basal Ganglia physiopathology
Basal Ganglia Diseases genetics
Basal Ganglia Diseases pathology
Basal Ganglia Diseases physiopathology
DNA Mutational Analysis
Diagnosis, Differential
Dystonia physiopathology
Epilepsy genetics
Epilepsy physiopathology
Female
Genetic Testing
Genotype
Humans
Inheritance Patterns genetics
Male
Middle Aged
Mitochondrial Diseases physiopathology
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Muscle, Skeletal physiopathology
Optic Atrophy, Hereditary, Leber genetics
Pedigree
RNA, Transfer genetics
DNA, Mitochondrial genetics
Dystonia genetics
Genetic Predisposition to Disease genetics
Mitochondrial Diseases diagnosis
Mitochondrial Diseases genetics
Mutation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1526-632X
- Volume :
- 69
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Neurology
- Publication Type :
- Academic Journal
- Accession number :
- 17724295
- Full Text :
- https://doi.org/10.1212/01.wnl.0000267843.10977.4a