title: A mitochondrial tRNA anticodon swap associated with a muscle disease.
abstract: We have identified an unusual mitochondrial (mt) tRNA mutation in a seven year-old girl with a pure myopathy. This G to A transition at mtDNA position 15990 changed the anticodon normally found in proline tRNAs (UGG) to the one found in serine tRNAs (UGA), and is the first pathogenic anticodon alteration described in a higher eukaryote. The mutant mtDNA was heteroplasmic (85% mutant) in muscle but was undetectable in white blood cells from the patient and her mother. Analysis of single muscle fibres indicated that mutant mtDNAs severely impaired mitochondrial protein synthesis and respiratory chain activity, but only when present at greater than 90%. The recessive behaviour of this mtDNA alteration may explain the patient's relatively mild clinical phenotype.
authors.affiliation: Department of Genetic, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
authors.forename: C T
authors.initials: CT
authors.lastname: Moraes
authors.forename: F
authors.initials: F
authors.lastname: Ciacci
authors.forename: E
authors.initials: E
authors.lastname: Bonilla
authors.forename: V
authors.initials: V
authors.lastname: Ionasescu
authors.forename: E A
authors.initials: EA
authors.lastname: Schon
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000926:Anticodon / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009132:Muscles / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012361:RNA, Transfer, Pro / Q000235:genetics; D012362:RNA, Transfer, Ser / Q000235:genetics; D014018:Tissue Distribution
chemical_list: D000926:Anticodon; D004272:DNA, Mitochondrial; D009124:Muscle Proteins; D000077278:RNA, Mitochondrial; D012361:RNA, Transfer, Pro; D012362:RNA, Transfer, Ser; D012313:RNA