Neuromuscular disease presentation with three genetic defects involving two genomes

Neuromuscul Disord. 2009 Dec;19(12):841-4. doi: 10.1016/j.nmd.2009.10.001. Epub 2009 Oct 22.


An extensive range of molecular defects have been identified in the human mitochondrial genome (mtDNA), many associated with well-characterised, progressive neurological syndromes. We describe a patient who presented to a mitochondrial clinic with progressive bilateral ptosis, external opthalmoplegia and increasing difficulty with walking. He had previously been diagnosed with a dominant, demyelinating polyneuropathy due to PMP22 gene duplication and had also developed gout, presenting in acute renal failure, due to an X-linked recessive HPRT gene mutation. Muscle biopsy revealed many COX-deficient fibres which we show contain high levels of a third genetic defect--a novel, mitochondrial tRNA(Leu(CUN)) (MTTL2) gene mutation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electron Transport Complex IV / metabolism
  • Gene Duplication
  • Genes, X-Linked
  • Genome, Human
  • Genome, Mitochondrial
  • Humans
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Male
  • Muscle, Skeletal / metabolism
  • Myelin Proteins / genetics*
  • Neuromuscular Diseases / genetics*
  • Neuromuscular Diseases / metabolism
  • Phenotype
  • RNA, Transfer, Amino Acyl / genetics*


  • Myelin Proteins
  • PMP22 protein, human
  • RNA, Transfer, Amino Acyl
  • Electron Transport Complex IV
  • Hypoxanthine Phosphoribosyltransferase