Clinical Features of Chinese Sporadic Leber Hereditary Optic Neuropathy Caused by Rare Primary mtDNA Mutations

J Neuroophthalmol. 2020 Mar;40(1):30-36. doi: 10.1097/WNO.0000000000000799.


Objective: The primary aim of this study was to describe clinical features of Chinese sporadic Leber hereditary optic neuropathy (LHON) caused by rare primary mitochondrial DNA (mtDNA) mutations.

Methods: We characterized a Chinese patient cohort with rare primary mtDNA mutations at Beijing Tongren Hospital between 2015 and 2018. The clinical features of these patients were retrospectively recorded and analyzed.

Results: Sixteen patients with LHON who had the selected rare primary mutations, including m.4171C>A (3 patients), m.10197G>A (1 patient), m.14459G>A (4 patients), and m.14502T>C (8 patients), were evaluated. The mean age at disease onset was 15 ± 6 years, and the male to female ratio was 15:1. Of 32 eyes of all patients, 75% (24/32) had a worst Snellen best-corrected visual acuity ≤0.1 (worse than 20/200), while 67% (2/3) who were carrying the m.4171C>A mutation experienced significant visual improvement. In addition, 40% (2/5) of patients with LHON carrying only m.14502T>C mutation had only mild visual impairment. Isolated manifestations of LHON was present in 94% (15/16) of all patients; 1 patient with the m.14459G>A mutation had LHON plus dystonia. Brain MRI T2 short tau inversion recovery sequences demonstrated optic atrophy in 62.5% (10/16); increased T2 signal in the optic nerve was found in 38% (6/16) of patients. The patient with LHON plus dystonia demonstrated optic atrophy and increased T2 signal in basal ganglia.

Conclusion: Patients with LHON and rare primary mutations have diverse clinical phenotypes. Those with the m.4171C>A mutation are more likely to have a good visual prognosis, while the m.14502T>C mutation may play a synergistic role in disease onset. Increased signal in the optic nerve on MRI is not rare, and this feature should not exclude LHON as the potential cause for optic neuropathy.

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Child
  • Child, Preschool
  • China
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Male
  • Mutation*
  • Optic Atrophy, Hereditary, Leber / diagnosis*
  • Optic Atrophy, Hereditary, Leber / genetics
  • Phenotype*
  • Retrospective Studies
  • Young Adult


  • DNA, Mitochondrial