PT  - JOURNAL ARTICLE
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
TI  - Novel <em>POLG1</em> mutations associated with neuromuscular and liver phenotypes in adults and children
AID  - 10.1136/jmg.2008.058180
DP  - 2009 Mar 01
TA  - Journal of Medical Genetics
PG  - 209--214
VI  - 46
IP  - 3
4099  - http://jmg.bmj.com/content/46/3/209.short
4100  - http://jmg.bmj.com/content/46/3/209.full
SO  - J Med Genet2009 Mar 01; 46
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.