Disorders associated with multiple deletions of mitochondrial DNA.
Brain Pathol
; 2(2): 133-9, 1992 Apr.
Article
em En
| MEDLINE
| ID: mdl-1341954
ABSTRACT
Multiple deletions of mitochondrial DNA (mtDNA) have recently been described in a number of patients with neurological disorders. Most cases have been clinically characterized by autosomal dominant inheritance, adult onset, and a slowly progressive course with external ophthalmoplegia and muscle weakness. Some patients have had evidence of central or peripheral nervous system involvement or episodes of myoglobinuria. Muscle biopsy findings include ragged-red fibres (RRF), muscle fibres with absent COX-activity and abundant abnormal mitochondria with paracrystalline inclusions. Biochemically, a generalized reduction in the activities of mtDNA-encoded enzymes is observed in skeletal muscle. Southern blotting or PCR analysis reveal multiple populations of deleted mtDNA. The deletions occur at multiple sites between the replication initiation sites, involving a large portion of mtDNA, and most deletions seem to be flanked by direct sequence repeats, shown to be "hot spots" in the case of single large deletions. Apparently, a defect in a nuclear gene results in multiple deletions of mtDNA. Both clinical, genetic and molecular genetic observations indicate heterogeneity of this new disease category, apparently based on a disturbance in the "cross-talk" between the nuclear and the mitochondrial genomes.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
/
Deleção de Sequência
/
Encefalomiopatias Mitocondriais
/
Complexo IV da Cadeia de Transporte de Elétrons
Tipo de estudo:
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article