RT Journal Article SR Electronic T1 Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 209 OP 214 DO 10.1136/jmg.2008.058180 VO 46 IS 3 A1 J D Stewart A1 S Tennant A1 H Powell A1 A Pyle A1 E L Blakely A1 L He A1 G Hudson A1 M Roberts A1 D du Plessis A1 D Gow A1 L D Mewasingh A1 M G Hanna A1 S Omer A1 A A Morris A1 R Roxburgh A1 J H Livingston A1 R McFarland A1 D M Turnbull A1 P F Chinnery A1 R W Taylor YR 2009 UL http://jmg.bmj.com/content/46/3/209.abstract AB Background: The POLG1 gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA replication and repair. Mutations in POLG1 have been linked to a spectrum of clinical phenotypes, and may account for up to 25% of all adult presentations of mitochondrial disease.Methods and results: We present 14 patients, with characteristic features of mitochondrial disease including progressive external ophthalmoplegia (PEO) and Alpers–Huttenlocher syndrome and laboratory findings indicative of mitochondrial dysfunction, including cytochrome c oxidase (COX) deficiency and multiple deletions or depletion of the mitochondrial DNA. Four novel POLG1 missense substitutions (p.R597W, p.L605R, p.G746S, p.A862T), are described, together with the first adult patient with a recently described polymerase domain mutation (p.R1047W). All novel changes were rare in a control population and affected highly conserved amino acids.Conclusion: The addition of these substitutions—including the first report of a dinucleotide mutation (c.1814_1815TT>GC)—to the growing list of defects further confirms the importance of POLG1 mutations as the underlying abnormality in a range of neurological presentations.