Article Text

Download PDFPDF
The 13042G→A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype
  1. M L Valentino1,
  2. P Barboni2,
  3. C Rengo3,
  4. A Achilli3,
  5. A Torroni3,
  6. R Lodi4,
  7. C Tonon4,
  8. B Barbiroli4,
  9. F Fortuna1,
  10. P Montagna1,
  11. A Baruzzi1,
  12. V Carelli1
  1. 1Dipartimento di Scienze Neurologiche, Università di Bologna, Bologna, Italy
  2. 2Centro Oftalmologia Salus, Bologna, Italy
  3. 3Dipartimento di Genetica e Microbiologia, Università di Pavia, Pavia, Italy
  4. 4Dipartimento di Medicina Clinica e Biotecnologia Applicata “D Campanacci”, Università di Bologna, Bologna, Italy
  1. Correspondence to:
 Dr Valerio Carelli
 Dipartimento di Scienze Neurologiche, Università di Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy; carelli{at}


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.

  • FID, free induction decay
  • LHON, Leber’s hereditary optic neuropathy
  • MELAS, mitochondrial encephalomyopathy, lactic acidosis, stroke-like syndrome
  • MERRF, myoclonic epilepsy, ragged red fibres
  • mtDNA, mitochondrial DNA
  • PCr, phosphocreatine
  • LHON
  • complex I
  • mtDNA
  • ND5
  • mitochondria

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Conflicts of interest: none declared