{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:16:44Z","timestamp":1790839004530,"version":"4.1.0"},"reference-count":27,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:sec>\n                  <jats:title>Background:<\/jats:title>\n                  <jats:p>The <jats:italic>POLG1<\/jats:italic> gene encodes the catalytic subunit of DNA polymerase gamma, essential for mitochondrial DNA replication and repair. Mutations in <jats:italic>POLG1<\/jats:italic> have been linked to a spectrum of clinical phenotypes, and may account for up to 25% of all adult presentations of mitochondrial disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results:<\/jats:title>\n                  <jats:p>We present 14 patients, with characteristic features of mitochondrial disease including progressive external ophthalmoplegia (PEO) and Alpers\u2013Huttenlocher syndrome and laboratory findings indicative of mitochondrial dysfunction, including cytochrome <jats:italic>c<\/jats:italic> oxidase (COX) deficiency and multiple deletions or depletion of the mitochondrial DNA. Four novel <jats:italic>POLG1<\/jats:italic> 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion:<\/jats:title>\n                  <jats:p>The addition of these substitutions\u2014including the first report of a dinucleotide mutation (c.1814_1815TT&gt;GC)\u2014to the growing list of defects further confirms the importance of <jats:italic>POLG1<\/jats:italic> mutations as the underlying abnormality in a range of neurological presentations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.058180","type":"journal-article","created":{"date-parts":[[2009,2,27]],"date-time":"2009-02-27T13:49:01Z","timestamp":1235742541000},"page":"209-214","source":"Crossref","is-referenced-by-count":40,"title":["Novel <i>POLG1<\/i> mutations associated with neuromuscular and liver\u00a0phenotypes in adults and children"],"prefix":"10.1136","volume":"46","author":[{"given":"J 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