title: The 8,344 mutation in mitochondrial DNA: a comparison between the proportion of mutant DNA and clinico-pathologic findings.
abstract: Ten patients, two men and eight women with mitochondrial encephalomyopathy, had an A-G mutation at nucleotide pair 8,344 in the mitochondrial DNA, the most common genetic defect in myoclonus epilepsy with ragged-red fibers (MERRF). Eight patients had the clinical and pathologic characteristics of MERRF including myoclonus, seizures, cerebellar ataxia and myopathy with ragged-red fibers. Two patients had atypical symptoms such as early onset of fatal cardiac failure and late onset of rapid mental deterioration, respectively. The striking feature in our patients with the 8,344 mutation cardiac involvement and two developed progressive heart failure. In the typical MERRF patients, the proportion of mutant mitochondrial DNA in their skeletal muscles, quantified by a single strand conformation polymorphism analysis, was above 85%. However, there was no significant correlation between clinical severity, histopathological findings and the proportion of mutant mtDNA in muscle biopsy samples, suggesting that non-ragged-red fibers play an important role in the phenotype expression of the mutants.
authors.affiliation: Department of Laboratory Medicine, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ozawa
authors.forename: Y
authors.initials: Y
authors.lastname: Goto
authors.forename: R
authors.initials: R
authors.lastname: Sakuta
authors.forename: Y
authors.initials: Y
authors.lastname: Tanno
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
authors.forename: I
authors.initials: I
authors.lastname: Nonaka
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid
chemical_list: D004272:DNA, Mitochondrial; D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV