A Novel Mitochondrial MTND5 Frameshift Mutation Causing Isolated Complex I Deficiency, Renal Failure and Myopathy

Neuromuscul Disord. 2010 Feb;20(2):131-5. doi: 10.1016/j.nmd.2009.10.010. Epub 2009 Dec 16.


Isolated complex I deficiency is the most commonly reported enzyme defect in paediatric mitochondrial disorders, and may arise due to mutations in nuclear-encoded structural or assembly genes, or the mitochondrial genome. We present the clinical, biochemical and molecular genetic data in a young girl whose clinical picture is dominated by chronic renal failure, myopathy and persistent lactic acidosis. An isolated complex I deficiency in muscle was identified due to a novel mutation (m.12425delA) in the MTND5 gene. This single nucleotide deletion is heteroplasmic and detectable in several tissues from the proband but not her mother, suggesting a de novo mutation event. The description of the first frameshift mutation in a mitochondrial complex I gene affirms mitochondrial DNA mutations as an important cause of isolated complex I deficiency in children and the importance of whole mitochondrial genome sequencing in the diagnostic work-up to elucidate the underlying molecular genetic abnormality and provide important genetic advice.

Publication types

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

MeSH terms

  • Acidosis, Lactic / enzymology
  • Acidosis, Lactic / genetics
  • Acidosis, Lactic / physiopathology
  • Child
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / genetics
  • Female
  • Frameshift Mutation / genetics
  • Gene Deletion
  • Genotype
  • Humans
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / physiopathology
  • Mitochondrial Proteins / genetics*
  • Muscular Diseases / enzymology
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology
  • Renal Insufficiency / enzymology
  • Renal Insufficiency / genetics*
  • Renal Insufficiency / physiopathology


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • ND5 protein, human
  • Electron Transport Complex I