Abstract
We have identified a cluster of mitochondrial tRNALeu[UUR], mutations in a severe case of infantile myopathy. There were A to G transitions found at mtDNA positions 3259, 3261, 3266 and 3268. These point mutations change the anticodon arm and the anticodon UAA, normally found in tRNALeu[UUR], to UGA which is the one of the tRNAsSer[UCN]. This is the first anticodon alteration described in this tRNA. Another swap straight to the anticodon of tRNAPro alone was recently described in a less severe case [1]. Until now infantile myopathies have not been attributed to defined mtDNA alterations. This study reports for the first time mtDNA point mutations causing this early onset of a mitochondrial disorder. The apparent homoplasmy of these mutations and especially the location in the anticodon must be considered lethal, if the child would not have been respirated for 5 years from its birth. (Mol Cell Biochem 174: 231–236, 1997)
Similar content being viewed by others
References
Moraes CT, Ciacci F, Bonilla E, Ionasescu V, Schon EA, DiMauro S: A mitochondrial anticodon swap associated with a muscle disease. Nat Gen 4: 284–288, 1993
Bresolin N, Zeviani M, Bonilla E, Miller RH, Leech RW, Shanske S, DiMauro S.: Fatal infantile cytochrome c oxidase deficiency: Decrease of immunologically detectable enzyme in muscle. Neurology 35: 802– 812, 1985
DiMauro S, Mendell JR, Sahenk Z, Bachman D, Scarpa A, Scofield RM, Reiner C: Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome c oxidase deficiency. Neurology 30: 795– 804, 1980
Sengers RCA, Trijbels JMF, Bakkeren JAJM: Deficiency of cytochrome b and aa3 in muscle from a floppy infant with cytochrome c oxidase deficiency. Eur J Pediatr 141: 178–180, 1984
Yoon KL, Aprille JR, Ernst SG: Mitochondrial tRNAThr mutation in fatale infantile respiratory enzyme deficiency. Biochem Biophys Res Commun 176: 1112–1115, 1991
Zeviani M, Peterson P, Servidei S, Bonilla E, DiMauro S: Benign reversible muscle cytochrome c oxidase deficiency: a second case. Neurology 37: 64–67, 1987
Wallace DC, Zheng X, Lott MT, Shoffner JM, Hodge GA, Kelley RI, Epstein CM: Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55: 601–610, 1988
Goto YI, Megumo T, Tohyama J, Horai S, Nonaka I: A novel point mutation in the mitochondrial tRNALeu[UUR] gene in a family with mitochondrial myopathy. Ann Neurol 31: 672–675, 1992
Bindoff LA, Howell W, Poulton J, McCellough DA, Morten KJ, Lightowlers RN, Turnbull DM, Weber K: Abnormal tRNA processing associated with a novel tRNA mutation in mitochondrial DNA. A potential disease mechanism. J Biol Chem 268: 19559–19564, 1993
Moraes CT, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N, Lovelace RE: Two novel pathogenic point mutations affecting organelle number and protein synthesis. J Clin Invest 92: 2906–2915, 1993
DiMauro S, Nicholson JF, Hays AP, Eastwood AB, Papadimitriou A, Koenigsberger R, DeViro DC: Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency. Ann Neurol 14: 226–234, 1983
Tritschler HJ, Bonilla E, Lombes A, Andreetta F, Servidei S, Schneyder B, Miranda AF: Differential diagnosis of fatal and benign cytochrome c oxidase-deficient myopathies of infancy. Neurology 41: 300–305, 1991
Goto Y-I, Nonaka I, Horai S: A mutation in the tRNALeu[UUR] gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348: 651–653, 1990
Kobayashi Y, Momoi MY, Tominaga K, Momoi T, Nihei K, Yanagisawa M, Kagawa Y: A point mutation in the mitochondrial tRNA Leu[UUR] gene in MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke like episodes). Biochem Biophys Res Commun 173: 816– 822, 1990
Anderson S, Bankier AT, Barell BG, De Bruijn MH, Coulson AR, Drouin J, Eperon IC: Sequence and organisation of the human mitochondrial genome. Nature 290: 457–465, 1981
Schimmel PR: Aminoacyl-tRNA synthetases: general features and recognition of tRNAs. Annu Rev Biochem 48: 601–648, 1977
Normanly J, Abelson J: tRNA identity. Annu Rev Biochem 58: 1029– 1049, 1989
Schulman LH: Recognition of tRNAs by aminoacyl-tRNA synthetases. Prog Nucl Acid Res 41: 23–87, 1991
Schulman LH, Pelka H: Anticodon switches changes the identity of methionine and valine tRNAs. Science 242: 765–768, 1988
Kumazawa Y, Himeno H, Miura K, Watanabe K: Unilateral aminoacylation specifity between bovine mitochondria and eubacteria. J Biochem 109: 421–427, 1991
Chomyn A, Meola G, Bresolin N, Lai ST, Scarlato G, Attardi G: In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria. Mol Cell Biol 11: 2236–2244, 1991
Goto YI, Nanaka I, Horai S: A new mutation associated with mitochondrial myopathy, encephalopathy and lactic acidosis and stroke like episodes. Biochim Biophys Acta 1097: 238–240, 1991
Zeviani M, Gellera C, Antozzi C, Rimoldi M, Morandi L, Villani F, Tiranti V: Maternally inherited myopathy and cardiomyopathy: associated with mutation in mitochondrial tRNALeu[UUR]. Lancet 338: 143– 147, 1991
Koga Y, Davidson M, Schon EA, King MP: Fine mapping of mitochondrial RNAs derived from the mt DNA region containing a point mutation associated with MELAS. Nucl Acid Res 21: 657–662, 1992
Hess JF, Parisi MA, Bennet SL, Clayton DA: Impairment of mitochondrial transcription termination by a pointmutation associated with the MELAS subgroup of mitochondrial encephalopathies. Nature 351: 236–239, 1991
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Zanssen, S., Molnar, M., Schröder, J. et al. Multiple mitochondrial tRNAMLeu[UUR] mutations associated with infantile myopathy. Mol Cell Biochem 174, 231–236 (1997). https://doi.org/10.1023/A:1006864709515
Issue Date:
DOI: https://doi.org/10.1023/A:1006864709515