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Free keywords:
Adult
Base Sequence
Child, Preschool
DNA, Mitochondrial/chemistry/*genetics
Female
Humans
Infant
Infant, Newborn
MELAS Syndrome/genetics
MERRF Syndrome/genetics
Mitochondrial Encephalomyopathies/*genetics
Molecular Sequence Data
*Point Mutation
Polymerase Chain Reaction
RNA, Transfer/*genetics
RNA, Transfer, Cys/genetics
RNA, Transfer, Leu/genetics
RNA, Transfer, Lys/genetics
*Sequence Analysis, DNA
Abstract:
We have investigated nine children with infantile onset of mitochondrial myopathy and two adults with myoclonus epilepsy and ragged-red fibers (MERRF) and chronic progressive external ophthalmoplegia (CPEO), respectively. These patients lacked any of the previously known pathogenic tRNA mutations. Southern blot analysis of muscle mtDNA revealed no deletions. The tRNA genes of muscle mtDNA were sequenced. Restriction enzyme analysis of PCR fragments was performed to verify the presence of the mutations identified by automatic sequencing. Several tRNA mutations were found, but they were all homoplasmic. Furthermore, the mutations were either present in controls or did not change nucleotides conserved between species. This strongly suggests that none of the tRNA mutations identified in the 11 patients with mitochondrial encephalomyopathy was pathogenic. It can thus be concluded that mitochondrial tRNA mutations and mtDNA deletions probably are an infrequent cause of mitochondrial disorders in infants. Patients with MERRF and CPEO may lack both pathogenic point mutations of tRNA genes and deletions of mtDNA.
