title: Mitochondrial DNA mutations in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
abstract: The total sequences of mitochondrial DNA were determined in two patients with juvenile-onset mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) due to Complex I deficiency. Patients 1 and 2 had three and two unique point mutations, respectively, causing replacement of phylogenically conserved amino acids. A transition from G to A was found at nucleotide position 5601 in the alanine tRNA gene of Patient 2, and a transition from A to G was found at 3243 in the leucine (UUR) tRNA gene of both patients. The latter mutation located at the phylogenically conserved 5' end of the dihydrouridine loop of the tRNA molecule, and was present in two patients with adult-onset MELAS and absent in controls. These results indicate that a mass of mtDNA mutations including the A-to-G transition in the tRNA(Leu) gene is a genetic cause of MELAS.
authors.affiliation: Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Ino
authors.forename: K
authors.initials: K
authors.lastname: Ohno
authors.forename: T
authors.initials: T
authors.lastname: Ohbayashi
authors.forename: S
authors.initials: S
authors.lastname: Ikebe
authors.forename: T
authors.initials: T
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Ichiki
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: T
authors.initials: T
authors.lastname: Ozawa
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001482:Base Composition; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000235:genetics*; D008931:Mitochondria, Muscle / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D016660:NAD(P)H Dehydrogenase (Quinone); D009690:Nucleic Acid Conformation; D015345:Oligonucleotide Probes; D011808:Quinone Reductases / Q000172:deficiency / Q000235:genetics*; D012356:RNA, Transfer, Leu / Q000235:genetics; D013577:Syndrome
chemical_list: D004272:DNA, Mitochondrial; D015345:Oligonucleotide Probes; D012356:RNA, Transfer, Leu; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases