{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T10:56:40Z","timestamp":1761217000537,"version":"build-2065373602"},"reference-count":27,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2006,11]]},"abstract":"<jats:p>\n                  <jats:bold>Background:<\/jats:bold> Enzyme deficiencies of the oxidative phosphorylation (OXPHOS) system may be caused by mutations in the mitochondrial DNA (mtDNA) or in the nuclear DNA.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Objective:<\/jats:bold> To analyse the sequences of the mtDNA coding region in 25 patients with OXPHOS system deficiency to identify the underlying genetic defect.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results:<\/jats:bold> Three novel non-synonymous substitutions in protein-coding genes, 4681T\u2192C in MT-ND2, 9891T\u2192C in MT-CO3 and 14122A\u2192G in MT-ND5, and one novel substitution in the 12S rRNA gene, 686A\u2192G, were found. The definitely pathogenic mutation 3460G\u2192A was identified in an 18-year-old woman who had severe isolated complex I deficiency and progressive myopathy.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions:<\/jats:bold> Bioinformatic analyses suggest a pathogenic role for the novel 4681T\u2192C substitution found in a boy with Leigh\u2019s disease. These results show that the clinical phenotype caused by the primary Leber\u2019s hereditary optic neuropathy mutation 3460G\u2192A is more variable than has been thought. In the remaining 23 patients, the role of mtDNA mutations as a cause of the OXPHOS system deficiency could be excluded. The deficiency in these children probably originates from mutations in the nuclear genes coding for respiratory enzyme subunits or assembly factors.<\/jats:p>","DOI":"10.1136\/jmg.2006.042168","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T20:43:20Z","timestamp":1149108200000},"page":"881-886","source":"Crossref","is-referenced-by-count":21,"title":["Analysis of mitochondrial DNA sequences in patients with isolated or combined oxidative phosphorylation system deficiency"],"prefix":"10.1136","volume":"43","author":[{"given":"R","family":"Hinttala","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Smeets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J S","family":"Moilanen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Ugalde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Uusimaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J A M","family":"Smeitink","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Majamaa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2006,5,31]]},"reference":[{"key":"2025100521004825000_43.11.881.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022567"},{"key":"2025100521004825000_43.11.881.2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh259"},{"key":"2025100521004825000_43.11.881.3","doi-asserted-by":"publisher","DOI":"10.1038\/35047064"},{"key":"2025100521004825000_43.11.881.4","doi-asserted-by":"publisher","DOI":"10.1086\/320591"},{"key":"2025100521004825000_43.11.881.5","doi-asserted-by":"publisher","DOI":"10.1086\/339933"},{"key":"2025100521004825000_43.11.881.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00414-004-0427-6"},{"key":"2025100521004825000_43.11.881.7","doi-asserted-by":"publisher","DOI":"10.1101\/gr.2286304"},{"key":"2025100521004825000_43.11.881.8","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1534\/genetics.105.043901","volume":"172","year":"2006","journal-title":"Genetics"},{"key":"2025100521004825000_43.11.881.9","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msg121"},{"key":"2025100521004825000_43.11.881.10","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10734"},{"key":"2025100521004825000_43.11.881.11","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20570"},{"key":"2025100521004825000_43.11.881.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.04.055"},{"key":"2025100521004825000_43.11.881.13","doi-asserted-by":"publisher","DOI":"10.1038\/35072063"},{"key":"2025100521004825000_43.11.881.14","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1023\/A:1025960300710","volume":"26","year":"2003","journal-title":"J Inherit Metab"},{"key":"2025100521004825000_43.11.881.15","doi-asserted-by":"publisher","DOI":"10.1086\/302802"},{"key":"2025100521004825000_43.11.881.16","doi-asserted-by":"publisher","DOI":"10.1038\/13779"},{"key":"2025100521004825000_43.11.881.17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90059-N"},{"key":"2025100521004825000_43.11.881.18","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088434"},{"key":"2025100521004825000_43.11.881.19","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1992.01080230077025"},{"key":"2025100521004825000_43.11.881.20","doi-asserted-by":"publisher","DOI":"10.1007\/s004140100228"},{"key":"2025100521004825000_43.11.881.21","doi-asserted-by":"publisher","DOI":"10.1086\/375406"},{"key":"2025100521004825000_43.11.881.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cccn.2004.11.003"},{"key":"2025100521004825000_43.11.881.23","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.39.3.162"},{"key":"2025100521004825000_43.11.881.24","doi-asserted-by":"publisher","DOI":"10.1086\/375537"},{"key":"2025100521004825000_43.11.881.25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00573524","volume":"17","year":"1963","journal-title":"Doc Ophthalmol"},{"key":"2025100521004825000_43.11.881.26","doi-asserted-by":"crossref","unstructured":"Ugalde C, Hinttala R, Timal S, Smeets R, Rodenburg RJT, Uusimaa J, van Heuvel LP, Nijtmans LGJ, Majamaa K, Smeitink JAM. Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrsme. Mol Genet Metab 2006; [in press].","DOI":"10.1016\/j.ymgme.2006.08.003"},{"key":"2025100521004825000_43.11.881.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2004.07.006"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.2006.042168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:00:53Z","timestamp":1759723253000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.2006.042168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,31]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2006,11,3]]},"published-print":{"date-parts":[[2006,11]]}},"alternative-id":["10.1136\/jmg.2006.042168"],"URL":"https:\/\/doi.org\/10.1136\/jmg.2006.042168","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[2006,5,31]]}}}