RT Journal Article SR Electronic T1 The 13042G→A/ND5 mutation in mtDNA is pathogenic and can be associated also with a prevalent ocular phenotype JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP e38 OP e38 DO 10.1136/jmg.2005.037507 VO 43 IS 7 A1 M L Valentino A1 P Barboni A1 C Rengo A1 A Achilli A1 A Torroni A1 R Lodi A1 C Tonon A1 B Barbiroli A1 F Fortuna A1 P Montagna A1 A Baruzzi A1 V Carelli YR 2006 UL http://jmg.bmj.com/content/43/7/e38.abstract AB 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.