Novel mitochondrial transfer RNA(Phe) gene mutation associated with late-onset neuromuscular disease.
BACKGROUND
An extensive range of molecular defects have been identified in the human mitochondrial genome (mitochondrial DNA); many are associated with well-characterized, progressive neurological syndromes, but a minority of patients have uncharacteristic phenotypes in which symptoms may be relatively mild.


OBJECTIVE
To describe a novel transfer RNA(Phe) mutation of mitochondrial DNA in a late-onset case with a mild phenotype of mitochondrial disease.


METHODS
Case report.


METHODS
A 66-year-old woman presented with a 4-year history of walking difficulties due to exercise intolerance and paresthesia in the feet. Clinical examination results were normal. Her deceased mother had similar walking difficulties, but her sister and 2 children were unaffected.


RESULTS
The demonstration of a marked histochemical defect in cytochrome c oxidase activity on muscle biopsy prompted molecular investigation of mitochondrial DNA, revealing a novel maternally inherited mutation in the variable loop of the mitochondrial transfer RNA(Phe) gene. This 622G>A transition was heteroplasmic and segregated with cytochrome c oxidase deficiency in single fibers.


CONCLUSIONS
This case serves to illustrate that primary defects of the mitochondrial genome should be considered even in older patients with late-onset, mild neuromuscular symptoms.
Deschauer
Marcus
M
Department of Neurology, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.
Swalwell
Helen
H
Strauss
Maria
M
Zierz
Stephan
S
Taylor
Robert W
RW
D017668:Age of Onset; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D003576:Electron Transport Complex IV / Q000378:metabolism; D005260:Female; D006801:Humans; D046529:Microscopy, Electron, Transmission / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology; D010649:Phenylalanine / Q000235:genetics*; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012343:RNA, Transfer / Q000235:genetics*
D000077278:RNA, Mitochondrial; D010649:Phenylalanine; D012313:RNA; D012343:RNA, Transfer; D003576:Electron Transport Complex IV