title: OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background.
abstract: BACKGROUND
  Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations.
  
  
  METHODS
  To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs.
  
  
  RESULTS
  The comparison between patient and reference populations did not revealed any significant difference.
  
  
  CONCLUSIONS
  Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background).
authors.affiliation: Université Bordeaux 1, Laboratoire d'Anthropologie des Populations du Passé, UMR 5199 PACEA, 33400 Talence, France. d.pierron@anthropologie.u-bordeaux1.fr
authors.forename: Denis
authors.initials: D
authors.lastname: Pierron
authors.forename: Marc
authors.initials: M
authors.lastname: Ferré
authors.forename: Christophe
authors.initials: C
authors.lastname: Rocher
authors.forename: Arnaud
authors.initials: A
authors.lastname: Chevrollier
authors.forename: Pascal
authors.initials: P
authors.lastname: Murail
authors.forename: Didier
authors.initials: D
authors.lastname: Thoraval
authors.forename: Patrizia
authors.initials: P
authors.lastname: Amati-Bonneau
authors.forename: Pascal
authors.initials: P
authors.lastname: Reynier
authors.forename: Thierry
authors.initials: T
authors.lastname: Letellier
mesh_terms: D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005602:France; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D004272:DNA, Mitochondrial; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human