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
Prof. Dr. M. J. Schröder
Institut für Neuropathologie Universitätsklinikum RWTH Aachen
52074 Aachen
Germany
eMail: E-mail: m.schroeder@post.klinikum.rwth-aachen.de
