TY - JOUR T1 - Novel <em>POLG1</em> mutations associated with neuromuscular and liver phenotypes in adults and children JF - Journal of Medical Genetics JO - J Med Genet SP - 209 LP - 214 DO - 10.1136/jmg.2008.058180 VL - 46 IS - 3 AU - J D Stewart AU - S Tennant AU - H Powell AU - A Pyle AU - E L Blakely AU - L He AU - G Hudson AU - M Roberts AU - D du Plessis AU - D Gow AU - L D Mewasingh AU - M G Hanna AU - S Omer AU - A A Morris AU - R Roxburgh AU - J H Livingston AU - R McFarland AU - D M Turnbull AU - P F Chinnery AU - R W Taylor Y1 - 2009/03/01 UR - http://jmg.bmj.com/content/46/3/209.abstract N2 - 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&gt;GC)—to the growing list of defects further confirms the importance of POLG1 mutations as the underlying abnormality in a range of neurological presentations. ER -