Novel mitochondrial mutation in the ND4 gene associated with Leigh syndrome

Acta Neurol Scand. 2006 Nov;114(5):350-3. doi: 10.1111/j.1600-0404.2006.00673.x.


We analyzed the complete mitochondrial genome of a 3-month-old female child with basal ganglionic lesions and other clinical features suggestive of Leigh syndrome, which is caused by variations in mitochondrial and nuclear genes. Our study revealed a novel, homoplasmic T11984C missense mutation in ND4 gene, which replaces a highly conserved amino acid tyrosine with histidine. Computational analysis showed that this mutation alters the secondary structure of ND4 subunit. As the mutation observed in this study was novel and homoplasmic, we speculate that there could be interplay of this mitochondrial mutation along with nuclear gene(s) in the pathogenesis.

Publication types

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

MeSH terms

  • Amino Acid Sequence / genetics
  • Amino Acid Substitution / genetics
  • Basal Ganglia / pathology
  • Basal Ganglia / physiopathology
  • Basal Ganglia Diseases / genetics*
  • Basal Ganglia Diseases / pathology
  • Basal Ganglia Diseases / physiopathology
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Electron Transport Complex I / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Histidine / genetics
  • Humans
  • Infant
  • Leigh Disease / genetics*
  • Leigh Disease / pathology
  • Leigh Disease / physiopathology
  • Magnetic Resonance Imaging
  • Molecular Sequence Data
  • Mutation, Missense / genetics*
  • Protein Subunits / genetics
  • Tyrosine / genetics


  • DNA, Mitochondrial
  • Protein Subunits
  • Tyrosine
  • Histidine
  • Electron Transport Complex I