title: Secondary mutations of mitochondrial DNA in Japanese patients with Leber's hereditary optic neuropathy.
abstract: OBJECTIVE
  Based on studies on the pathogenesis of Leber's hereditary optic neuropathy (LHON), mitochondrial DNA (mtDNA) mutations have been divided into two types: primary and secondary. Primary mutations at nucleotide positions (nt) 11778, 3460, and 14484 can each cause LHON. Secondary mutations may be simultaneously found in LHON patients with a primary mutation, may occur at higher frequency in LHON patients than in normal controls, and may play an additional role in the pathogenesis of LHON. We examined the frequencies of secondary mutations of mtDNA at nt3394, 7444, 9438, 9804, 13708, and 15257 in 19 Japanese patients with LHON associated with primary mutations and 108 normal controls.
  
  
  METHODS
  Mutations were determined by restriction enzyme analysis or DNA sequencing using polymerase chain reaction (PCR) products.
  
  
  RESULTS
  One patient with an nt11778 mutation also had an nt13708 mutation. Another patient with an nt3460 mutation also had an nt7444 mutation. During DNA sequencing of the PCR fragment harboring nt3394, three novel mutations in the ND1 gene (nt3316, 3496, and 3497 mutations) were found in three patients with an nt11778 mutation. The frequency of these mutations in 108 control subjects was studied further: one (0.9%) had an nt3394 mutation, none (0%) had an nt9804 mutation, one (0.9%) had an nt13708 mutation, two (1.9%) had nt3316 mutations, one (0.9%) had an nt3496 mutation, and two (1.9%) had nt3497 mutations.
  
  
  CONCLUSIONS
  It is unlikely that the frequencies of secondary mutations in Japanese patients with LHON are higher than those in normal Japanese controls. It is possible that the mutations at nt3316, 3496, and 3497 are secondary mutations of LHON.
authors.affiliation: Toyama Medical and Pharmaceutical University, Department of Ophthalmology, Toyama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Hayasaka
authors.forename: C
authors.initials: C
authors.lastname: Kadoi
authors.forename: Y
authors.initials: Y
authors.lastname: Hotta
authors.forename: K
authors.initials: K
authors.lastname: Fujiki
authors.forename: T
authors.initials: T
authors.lastname: Fujimaki
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: S
authors.initials: S
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Kanai
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D015418:Optic Atrophies, Hereditary / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D004272:DNA, Mitochondrial