title: The 13042G --> A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype.
abstract: BACKGROUND
  Overlapping phenotypes including LHON, MELAS, and Leigh syndrome have recently been associated with numerous mtDNA point mutations in the ND5 gene of complex I, now considered a mutational hot spot.
  
  
  OBJECTIVE
  To identify the mtDNA defect in a family with a prevalent ocular phenotype, including LHON-like optic neuropathy, retinopathy, and cataract, but characterised also by strokes, early deaths, and miscarriages on the maternal line.
  
  
  RESULTS
  Sequencing of the entire mitochondrial genome from the proband's muscle DNA identified the heteroplasmic 13042G-->A transition, which was previously described only once in a patient with a different mitochondrial disease. This mutation fulfils the major pathogenic criteria, inducing an amino acid change (A236T) at an invariant position in a highly conserved domain of the ND5 gene. Phosphorus magnetic resonance spectroscopy in the proband disclosed an in vivo brain and skeletal muscle energy metabolism deficit.
  
  
  CONCLUSIONS
  These findings conclusively establish the pathogenic role of the 13042G-->A mutation and underscore its variable clinical expression.
authors.affiliation: Dipartimento di Scienze Neurologiche, Università di Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy.
authors.forename: M L
authors.initials: ML
authors.lastname: Valentino
authors.forename: P
authors.initials: P
authors.lastname: Barboni
authors.forename: C
authors.initials: C
authors.lastname: Rengo
authors.forename: A
authors.initials: A
authors.lastname: Achilli
authors.forename: A
authors.initials: A
authors.lastname: Torroni
authors.forename: R
authors.initials: R
authors.lastname: Lodi
authors.forename: C
authors.initials: C
authors.lastname: Tonon
authors.forename: B
authors.initials: B
authors.lastname: Barbiroli
authors.forename: F
authors.initials: F
authors.lastname: Fortuna
authors.forename: P
authors.initials: P
authors.lastname: Montagna
authors.forename: A
authors.initials: A
authors.lastname: Baruzzi
authors.forename: V
authors.initials: V
authors.lastname: Carelli
mesh_terms: D020137:Base Pair Mismatch; D001921:Brain / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D005128:Eye Diseases / Q000235:genetics*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
chemical_list: D004272:DNA, Mitochondrial