Clinical variability in maternally inherited leber hereditary optic neuropathy with the G14459A mutation

Am J Med Genet A. 2004 Feb 1;124A(4):372-6. doi: 10.1002/ajmg.a.20449.


Spasticity and dystonia have been associated with mitochondrial (mt) DNA mutations at A11696G, G14459A, and T14596A. We describe the clinical features and molecular analysis of two Caucasian pedigrees with the 14,459 guanosine (G) --> adenine (A) transition. The maternally inherited Leber hereditary optic neuropathy (LHON) phenotypes showed extreme clinical variability and the only screening test that was abnormal in the patient with spasticity/dystonia was a high T2 signal in the putamen bilaterally. The male patient in the second pedigree showed features of optic neuropathy without spasticity/dystonia. These results further support that the 14,459 G --> A transition mutation is causally related to LHON and spasticity/dystonia.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA, Mitochondrial / genetics*
  • Dystonia / diagnosis*
  • Dystonia / genetics
  • Female
  • Fibroblasts / chemistry
  • Humans
  • Male
  • Middle Aged
  • Muscle Spasticity / diagnosis*
  • Muscle Spasticity / genetics
  • Optic Atrophy, Hereditary, Leber / diagnosis*
  • Optic Atrophy, Hereditary, Leber / genetics
  • Pedigree
  • Point Mutation*
  • Putamen / metabolism


  • DNA, Mitochondrial