G.P.185

Mitochondrial DNA host a wide number of molecular defects associated with a broad spectrum of human clinical presentations ranging from tissue-specific diseases such as isolated myopathy or Leber hereditary optic neuropathy to multisystem disorders. Mutations affecting mitochondrial protein synthesis (transfer and ribosomal RNA genes) are quite frequent while molecular defects affecting genes encoding respiratory chain subunits are relatively less common. Here we discuss clinical, histological and molecular features of a patient presenting isolated myopathy secondary to mitochondrial complex I deficiency. Muscle biopsy showed ragged-red fibers that stained intensely for cytochrome c oxidase activity (COX-positive RRF). Muscle respiratory chain biochemical analysis revealed a severe (  A mutation, resulting in a premature termination codon within ND1 subunit. Mutational load was assessed by PCR-RFLP analysis and found to be 50% in skeletal muscle. Conversely we did not detect the variant in proband’s blood and proliferating cells including fibroblasts and myoblasts. To our knowledge, only two other non sense mutations have been reported in ND1 gene: the m.3308T > G mutation (p. M1X) in three cases of infantile onset sudden death syndromes and the intragenic inversion of seven nucleotides, resulting, similar to our proband, in isolated mitochondrial myopathy.