The 13042G→A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype
- Valentino, M L
- Barboni, P
- Rengo, C
- Achilli, A
- Torroni, A
- Lodi, R
- Tonon, C
- Barbiroli, B
- Fortuna, F
- Montagna, P
- Baruzzi, A
- Carelli, V
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.