In a recent edition of Brain, Tzoulis and colleagues (Tzoulis et al., 2006) described the presentation and natural history of neurological disease due to the c.1399G → A/A467T and c.2243G → C/W748S mutations in POLG. POLG codes for mitochondrial DNA (mtDNA) polymerase (pol γ), the only polymerase present within mitochondria (Kaguni, 2004).