title: A mutational hot spot in the mitochondrial ND6 gene in patients with Leber's hereditary optic neuropathy.
abstract: BACKGROUND
  Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by rapid bilateral loss of central vision. Most patients harbor one of three mutations in the mitochondrial DNA. In order to identify the genetic cause of the disease in one LHON patient without any of the three primary mutations, we sequenced the mitochondrial genome.
  
  
  METHODS
  Ophthalmological examination was performed in the affected person and his unaffected relatives. The complete mitochondrial protein coding region was sequenced in the patient.
  
  
  RESULTS
  Clinical examination of the affected 10-year-old Turkish boy showed typical features of LHON. Peripapillary microangiopathy was also seen in relatives of the maternal line. Sequence analysis revealed a point mutation at position 14482 in the mitochondrial ND6 gene that changes a conserved methionine residue to isoleucine. A mutation at this nucleotide position has been previously suggested to be of pathogenic significance and has not been detected in any controls.
  
  
  CONCLUSIONS
  We have identified that the mutation at nucleotide position 14482 which is the eight mutation in the ND6 gene that causes LHON, making this gene a hot spot for the disease. All eight identified mutations in the ND6 gene lie within the evolutionarily most conserved region of the ND6 gene in a hydrophobic pocket. This may help in understanding the pathomechanism of LHON.
authors.affiliation: Universitäts-Augenklinik Abt. II, Tübingen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Luberichs
authors.forename: Beate
authors.initials: B
authors.lastname: Leo-Kottler
authors.forename: Dorothea
authors.initials: D
authors.lastname: Besch
authors.forename: Sascha
authors.initials: S
authors.lastname: Fauser
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000235:genetics; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D058609:Visual Field Tests; D014794:Visual Fields
chemical_list: D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I