TY - JOUR 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 SP - e38 LP - e38 DO - 10.1136/jmg.2005.037507 VL - 43 IS - 7 AU - M L Valentino AU - P Barboni AU - C Rengo AU - A Achilli AU - A Torroni AU - R Lodi AU - C Tonon AU - B Barbiroli AU - F Fortuna AU - P Montagna AU - A Baruzzi AU - V Carelli Y1 - 2006/07/01 UR - http://jmg.bmj.com/content/43/7/e38.abstract N2 - 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. ER -