Oculopharyngeal somatic myopathy in a patient with a novel large-scale 3399 bp deletion and a homoplasmic T5814C transition of the mitochondrial DNA

We report a 65-year-old woman with a sporadic form of progressive oculopharyngeal somatic myopathy due to a novel large-scale 3399 base pair (bp) deletion of the mitochondrial DNA (mtDNA) and co-occurrence of a homoplasmic T5814C transition. The onset of myopathy began from chronic progressive external ophthalmoplegia (CPEO) at age of 20 years. Bulbar weakness, neck and proximal limb paralysis, slowly progressed to eventual respiratory failure. The plasma levels of pyruvate (1.5 mg/dL) and lactate (20.2 mg/dL) were elevated. Muscle biopsy showed decreased enzymatic activity of cytochrome c oxidase, but no ragged-red fibers. Electron microscopy showed "parking-lot" paracrystalline inclusions in the enlarged mitochondria suggestive for mitochondrial myopathy. Sequencing of the whole mitochondrial genome of the patient's muscle and leukocytes showed 3399 bp deletion of the mtDNA from nucleotide position 8024 to 11,423 and a homoplasmic thymidine to cytosine transition at nucleotide position 5814 of the tRNA^Cys gene of mtDNA (T5814C). T5814C was absent in the white blood cells of the patient's daughter and in 205 normal controls. We conclude that a large-scale deletion may coexist with T5814C transition in patients with sporadic form of mitochondrial cytopathy manifested by slowly progressive oculopharyngeal somatic myopathy.