title: Respiration-deficient cells are caused by a single point mutation in the mitochondrial tRNA-Leu (UUR) gene in mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS).
abstract: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) is a major subgroup of heterogeneous mitochondrial diseases. For identifying a mutation in the mitochondrial gene, we isolated, from the same muscle tissue from a patient with MELAS, cell lines with distinctly different phenotypes: one was respiration-deficient, and the other was apparently normal. Compared with the normal cells, only one A-to-G nucleotide transition at nucleotide 3243 in the tRNA-Leu (UUR) gene was found in whole mtDNA of the respiration-deficient cells. This mutation was also found in eight patients, from unrelated families, who had MELAS in a heteroplasmic manner but was not found in control individuals. Therefore, the single point mutation causes the functional abnormality in the respiratory chain of mitochondria.
authors.affiliation: Department of Pediatrics, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: M Y
authors.initials: MY
authors.lastname: Momoi
authors.forename: K
authors.initials: K
authors.lastname: Tominaga
authors.forename: H
authors.initials: H
authors.lastname: Shimoizumi
authors.forename: K
authors.initials: K
authors.lastname: Nihei
authors.forename: M
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: S
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000140:Acidosis, Lactic / Q000235:genetics; D044466:Asian People; D001483:Base Sequence; D001927:Brain Diseases / Q000235:genetics; D002460:Cell Line; D002561:Cerebrovascular Disorders / Q000235:genetics; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009135:Muscular Diseases / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D004272:DNA, Mitochondrial; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D012313:RNA