Novel Cluster of tRNA ^{Leu (UUR)} Mutations in a Sporadic Case of Infantile Myopathy Restricted to Muscle Tissue

In a previous study we reported on a case with severe infantile, mitochondrial myopathy caused by somatic mutation [[12]]. In the present study we give evidence for asymmetric tissue distribution of the mutations. Mitochondrial DNA (mtDNA) analysis showed a cluster of nearly homoplasmic point mutations in the tRNA gene for leucine (UUR) (A3259 G, A3261 G, A3266 G, A3268 G). The mutation is abundant in muscle, but is not found in blood cells. This cluster of mutations is sporadic, because the search for mutant molecules in the blood of the healthy mother and maternal grandmother did not show these alterations.

Key words

mtDNA - Mitochondrial tRNALeu(UUR) - Infantile myopathy

References

• 1 Anderson S, de Bruijn M H, Coulson A R, Eperon I C, Sanger F, Young I G. Complete sequence of bovine mitochondrial DNA. Conserved features of the mammalian mitochondrial genome.  J Mol Biol. 1982;  156 683-717
• 2 Brown W M, Prager E M, Wang A, Wilson A C. Mitochondrial DNA sequences of primates: tempo and mode of evolution.  J Mol Evol. 1982;  18 225-239
• 3 Degoul F, François D, Diry M, Ponsot G, Desguerre I, Heron B. et al . A near homoplasmic T8993 G mtDNA mutation in a patient with atypic Leigh syndrome not present in the mother's tissues.  J Inherit Metab Dis. 1997;  20 49-53
• 4 Fu K, Hartlen R, Johns T, Genge A, Karpati G, Shoubridge E A. A novel heteroplasmic tRNALeu(CUN) mtDNA point mutation in a sporadic patient with mitochondrial encephalomyopathy segregates rapidly in skeletal muscle and suggests an approach to therapy.  Hum Mol Genet. 1996;  5 1835-1840
• 5 Hammans S R, Sweeney M G, Brockington M, Morgan-Hughes J A, Harding A E. Mitochondrial encephalopathies: molecular genetic diagnosis from blood samples.  Lancet. 1991;  337 1311-1313
• 6 Holt I J, Harding A E, Morgan-Hughes J A. Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies.  Nature. 1988;  331 717-719
• 7 Jenuth J P, Peterson A C, Shoubridge E A. Tissue-specific selection for different mtDNA genotypes in heteroplasmic mice.  Nat Genet. 1997;  16 93-95
• 8 Servidei S. Mitochondrial encephalomyopathies: Gene mutation.  Neuromusc Discord. 2000;  10 XI-XIII
• 9 Moraes C T, Ciacci F, Bonilla E, Ionasescu V, Schon E A, DiMauro S. A mitochondrial tRNA anticodon swap associated with a muscle disease.  Nat Genet. 1993;  4 284-288
• 10 Moraes C T, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N. et al . Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu[UUR]) gene an etiologic hot spot?.  J Clin Invest. 1993;  92 2906-2915
• 11 Nakamura M, Nakano S, Goto Y, Ozawa M, Nagahama Y, Fukuyama H. et al . A novel point mutation in the mitochondrial tRNA(Ser[UCN]) gene detected in a family with MERRF/MELAS overlap syndrome.  Biochem Biophys Res Commun. 1995;  214 86-93
• 12 Zanssen S, Molnar M, Schröder J M, Buse G. Multiple mitochondrial tRNA(Leu[UUR]) mutations associated with infantile myopathy.  Mol Cell Biochem. 1997;  174 231-236