title: A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset mitochondrial encephalomyopathy.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) mutations are increasingly being recognized as causes of late-onset disease. We report a patient with a late-onset mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at position 5556 in the gene encoding the tRNA for tryptophan (MTTW).
  
  
  OBJECTIVE
  To investigate the cause of disease and assess the pathogenicity of this new mutation.
  
  
  METHODS
  Clinical, histopathological and gene sequencing studies. Quantification of the mutation was performed in different tissues from the patient and two relatives and in single muscle fibres.
  
  
  RESULTS
  The mutation was heteroplasmic, segregated in biochemically affected muscle fibres and was absent in blood. The level of mutation in skeletal muscle was higher than in brain, although the brain was clinically the most affected tissue.
  
  
  CONCLUSIONS
  The 5556G > C mutation appears sporadic. It was not found in any of the family members tested, although some of them manifested disorders that can be associated with mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case illustrates the challenges posed when assigning pathogenicity to mtDNA mutations.
authors.affiliation: Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: P S
authors.initials: PS
authors.lastname: Sanaker
authors.forename: H L
authors.initials: HL
authors.lastname: Nakkestad
authors.forename: E
authors.initials: E
authors.lastname: Downham
authors.forename: L A
authors.initials: LA
authors.lastname: Bindoff
mesh_terms: D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017237:Mitochondrial Encephalomyopathies / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009690:Nucleic Acid Conformation; D010375:Pedigree; D017354:Point Mutation; D012364:RNA, Transfer, Trp / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: D004272:DNA, Mitochondrial; D012364:RNA, Transfer, Trp