title: High Mitochondrial DNA Copy Number Is a Protective Factor From Vision Loss in Heteroplasmic Leber's Hereditary Optic Neuropathy (LHON).
abstract: OBJECTIVE
  Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance.
  
  
  METHODS
  We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated.
  
  
  RESULTS
  The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected.
  
  
  CONCLUSIONS
  The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON.
authors.affiliation: Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Ospedale 'Casa Sollievo della Sofferenza' IRCCS, UOC Genetica Medica, San Giovanni Rotondo, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Bisceglia
authors.affiliation: Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Russo
authors.affiliation: Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari, Italy.
authors.forename: Luigi L
authors.initials: LL
authors.lastname: Palese
authors.affiliation: Ospedale 'Casa Sollievo della Sofferenza' IRCCS, UOC Genetica Medica, San Giovanni Rotondo, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Agruma
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular; CIBERER, IIS-Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Emperador
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular; CIBERER, IIS-Aragón, Universidad de Zaragoza, Zaragoza, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.affiliation: Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Guerriero
authors.affiliation: Dipartimento di Scienze Mediche di Base, Neuroscienze e Organi di Senso - Università degli Studi Aldo Moro, Piazza G. Cesare, Bari, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use; D001766:Blindness / Q000517:prevention & control*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000627:therapeutic use; D014792:Visual Acuity
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D014451:Ubiquinone; C036619:idebenone