A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family

Biochem Biophys Res Commun. 2005 Jul 15;332(4):1115-21. doi: 10.1016/j.bbrc.2005.05.059.


Leber's hereditary optic neuropathy (LHON) is a frequent cause of inherited blindness. A routine screening for common mtDNA mutations constitutes an important first in its diagnosis. However, a substantial number of LHON patients do not harbor known variants, both pointing to the genetic heterogeneity of LHON and bringing into question its genetic diagnosis. We report a familial case that exhibited typical features of LHON but lacked any of the common mutations. Genetic analysis revealed a novel pathogenic defect in the ND6 gene at 14279A that was not detected in any haplogroup-matched controls screened for it, nor has it been previously reported. This mutation causes a substantial conformational change in the secondary structure of the polypeptide matrix coil and may explain the LHON expression. Thus, it expands the spectrum of deleterious changes affecting ND6-encoding subunit and further highlights the functional significance of this gene, providing additional clues to the disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Animals
  • DNA Mutational Analysis
  • DNA, Mitochondrial* / genetics
  • Family Health
  • Female
  • Haplotypes
  • Humans
  • Leucine / chemistry
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation*
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Pedigree
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Protein Conformation
  • Protein Structure, Secondary
  • Species Specificity
  • Whites


  • DNA, Mitochondrial
  • Leucine