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A tRNAAla mutation causing mitochondrial myopathy clinically resembling myotonic dystrophy
  1. R Horváth1,*,
  2. H Lochmüller2,*,
  3. C Scharfe3,
  4. B H Do3,
  5. P J Oefner3,
  6. J Müller-Höcker4,
  7. B G Schoser2,
  8. D Pongratz2,
  9. D P Auer5,
  10. M Jaksch1
  1. 1Metabolic Disease Centre Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics; Academic Hospital Schwabing, Munich; Germany
  2. 2Friedrich-Baur-Institut, Department of Neurology, Ludwig-Maximilians-University, Munich, Germany
  3. 3Stanford University, Genome Technology Center, Palo Alto, CA, USA
  4. 4Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany
  5. 5Max Planck Institute of Psychiatry, Munich, Germany
  1. Correspondence to:
 Dr M Jaksch
 Metabolic Disease Centre Munich-Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Academic Hospital Schwabing, Kölner Platz 1, 80804 München, Germany;

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More than 100 pathogenic mitochondrial (mt) DNA mutations have been described in the past decade in association with different neuromuscular disorders. Apart from large scale mtDNA rearrangements and common point mutations in mt tRNA genes, pathogenic mutations affecting structural genes of mtDNA encoded respiratory chain subunits have been reported as well.1

Pathogenic tRNA mutations can affect translation of respiratory chain (RC) complexes that are partly encoded by the mtDNA, that is, complexes I, III, and IV. The most common tRNA mutation is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and is located in the tRNALeu(UUR) gene. So far, 13 additional pathogenic mutations have been described in this gene in association with different neurodegenerative disorders. Similarly, mutations in tRNAIle, tRNALys, and tRNASer(UCN) are known to cause various mitochondrial encephalomyopathies or non-syndromic deafness (see Mitomap The remaining 18 mitochondrially encoded tRNAs are rarely reported to be mutated in mitochondrial disorders.2 In tRNAAla only one pathogenic mutation is listed in Mitomap to date. This mutation was found in an Italian patient who presented with late onset progressive external ophthalmoplegia and dysphagia.3 Another heteroplasmic G>A mutation at position 5650 of mt tRNAAla was described in addition to a Notch3 mutation in a 53 year old patient with typical symptoms of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) together with symptoms of a myopathy with numerous ragged red fibres.4 Therefore, the authors suggested a pathogenic role for both, the Notch3 and the tRNAAla G5650A mutation. However, the G5650A mutation has not been reported to any mitochondrial database.

Here we report a patient suffering from a novel type of mitochondrial myopathy resembling muscular dystrophy associated with the heteroplasmic G5650A mutation in the mtDNA encoded tRNAAla …

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  • * The first two authors contributed equally to this work.