title: Leber hereditary optic neuropathy. Electron microscopy and molecular genetic analysis of a case.
abstract: BACKGROUND
  Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disorder characterized by bilateral central visual loss typically in early adulthood. Few histopathologic studies, including ultrastructural and molecular genetic analysis, have been reported.
  
  
  METHODS
  Ocular tissue was obtained postmortem from an 81-year-old woman with LHON from the Queensland 1 pedigree characterized by mutations at nucleotide positions 4160 and 14484. Routine histopathologic studies, electron microscopy, electron-probe analysis, and molecular genetic analysis were performed.
  
  
  RESULTS
  Marked atrophy of the nerve fiber and retinal ganglion cell layers and optic nerves was present. Results of electron microscopic examination demonstrated 1.2 microns electron-dense, double-membrane-bound inclusions, consisting of calcium by electron-probe analysis, in retinal ganglion cells. The optic nerve was homoplasmic for mutations 4160 and 14484.
  
  
  CONCLUSIONS
  Optic nerve and inner retinal atrophy in LHON may be a result of metabolic mitochondrial dysfunction leading to intramitochondrial calcification. Homoplasmy for mitochondrial mutations 4160 and 14484 in the leukocyte/platelet fraction of whole blood may correlate with homoplasmy in the optic nerve.
authors.affiliation: Wilmer Eye Institute, Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Kerrison
authors.forename: N
authors.initials: N
authors.lastname: Howell
authors.forename: N R
authors.initials: NR
authors.lastname: Miller
authors.forename: L
authors.initials: L
authors.lastname: Hirst
authors.forename: W R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D002114:Calcinosis / Q000209:etiology / Q000473:pathology; D002118:Calcium / Q000032:analysis; D004272:DNA, Mitochondrial / Q000032:analysis; D004577:Electron Probe Microanalysis; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D008967:Molecular Biology; D009412:Nerve Fibers / Q000648:ultrastructure; D015418:Optic Atrophies, Hereditary / Q000235:genetics* / Q000473:pathology*; D009900:Optic Nerve / Q000648:ultrastructure; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012164:Retinal Diseases / Q000209:etiology / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D004272:DNA, Mitochondrial; D002118:Calcium