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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}neuro.unibo.it

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.

  • 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

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Footnotes

  • Conflicts of interest: none declared

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