RESUMO
A 14-year-old boy had exercise intolerance, weakness, ataxia, and lactic acidosis. Because his muscle biopsy showed a mosaic pattern of fibers staining intensely with the succinate dehydrogenase reaction but not at all with the cytochrome c oxidase reaction, we sequenced his mitochondrial DNA and found a novel mutation (C14680A) in the gene for tRNAGlu. The mutation was present in accessible tissues from the asymptomatic mother but not from a brother with Asperger syndrome. These data expand the clinical heterogeneity of mutations in this mitochondrial gene.
Assuntos
Deficiência de Citocromo-c Oxidase/genética , DNA Mitocondrial/genética , Encefalomiopatias Mitocondriais/genética , Músculo Esquelético/metabolismo , RNA de Transferência de Ácido Glutâmico/genética , Adolescente , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Masculino , Encefalomiopatias Mitocondriais/metabolismo , Encefalomiopatias Mitocondriais/patologia , Músculo Esquelético/patologia , Mutação , Polimorfismo de Nucleotídeo Único , RNA de Transferência de Ácido Glutâmico/metabolismoRESUMO
A 6-year-old boy had progressive muscle weakness since age 4 and emotional problems diagnosed as Asperger syndrome. His mother and two older siblings are in good health and there is no family history of neuromuscular disorders. Muscle biopsy showed ragged-red and cytochrome coxidase (COX)-negative fibers. Respiratory chain activities were reduced for all enzymes containing mtDNA-encoded subunits, especially COX. Sequence analysis of the 22 tRNA genes revealed a novel G10406A base substitution, which was heteroplasmic in multiple tissues of the patient by RFLP analysis (muscle, 96%; urinary sediment, 94%; cheek mucosa, 36%; blood, 29%). The mutation was not detected in any accessible tissues from his mother or siblings. It appears that this mutation arose de novo in the proband, probably early in embryogenesis.
Assuntos
DNA Mitocondrial/genética , Miopatias Mitocondriais/genética , RNA de Transferência de Arginina/genética , Substituição de Aminoácidos , Síndrome de Asperger/complicações , Criança , Humanos , Masculino , Miopatias Mitocondriais/complicações , Miopatias Mitocondriais/patologia , Conformação de Ácido Nucleico , Linhagem , Polimorfismo de Fragmento de Restrição , RNA de Transferência de Arginina/químicaRESUMO
OBJECTIVE: To document novel homozygous mutations in the gene for deoxyguanosine kinase (DGK) in 3 children with mitochondrial DNA depletion. DESIGN: Clinical features included liver failure, hypotonia, and nystagmus in 2 siblings, and liver cirrhosis, optic dysplasia, nystagmus, and microcephaly in the third patient. We sequenced the whole coding region of the DGK gene. RESULTS: We identified 2 novel homozygous mutations, G352A and C269T, that lead to truncated proteins. CONCLUSION: These data confirm that DGK mutations typically affect the liver and brain.