title: Genetic biochemical and pathophysiological characterization of a familial mitochondrial encephalomyopathy (MERRF).
abstract: Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome is a neuromuscular disorder characterized by mitochondrial myopathy and progressive myoclonus epilepsy. A heteroplasmic A to G transition mutation in the mitochondrial encoded tRNA(Lys) gene at nucleotide pair 8344 has been suggested to be linked to the MERRF-syndrome. We have investigated biochemically and histochemically muscle biopsies and studied the mitochondrial genomes of hair, blood and muscle tissue of a family including three cases of MERRF-syndrome as well as unaffected relatives within the maternal lineage. Sequence analysis of the mtDNAs, performed after amplification by the polymerase chain reaction (PCR), confirmed the A to G transition mutation in the tRNA(Lys) gene at position 8344. The additional point mutation at nucleotide pair 750 in the 12 S rRNA gene, which was also found by Shoffner et al. (1990), however, was absent in all investigated tissues. Quantitative analysis of the percentage of mutated mtDNA by mispairing PCR (Seibel et al., 1990) revealed variable contents in different tissues and individuals, including unaffected family members. Mitochondrial protein synthesis in cultured fibroblasts from MERRF patients revealed diminished incorporation of 35S-methionine into lysine-containing peptides.
authors.affiliation: Fachbereich Chemie, Philipps Universität, Marburg, F.R.G.
authors.forename: P
authors.initials: P
authors.lastname: Seibel
authors.forename: F
authors.initials: F
authors.lastname: Degoul
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: N
authors.initials: N
authors.lastname: Romero
authors.forename: D
authors.initials: D
authors.lastname: François
authors.forename: M
authors.initials: M
authors.lastname: Paturneau-Jouas
authors.forename: F
authors.initials: F
authors.lastname: Ziegler
authors.forename: B
authors.initials: B
authors.lastname: Eymard
authors.forename: M
authors.initials: M
authors.lastname: Fardeau
authors.forename: C
authors.initials: C
authors.lastname: Marsac
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009132:Muscles / Q000473:pathology; D009154:Mutation; D009690:Nucleic Acid Conformation; D010101:Oxygen Consumption; D012357:RNA, Transfer, Lys / Q000235:genetics*; D012016:Reference Values; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D012357:RNA, Transfer, Lys; D013384:Succinate Cytochrome c Oxidoreductase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase