{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:32:19Z","timestamp":1790839939534,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T00:00:00Z","timestamp":1382659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Brain and Behavior"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:p><jats:bold>Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ATP6<\/jats:styled-content><\/jats:italic> gene are reported to be associated with Leber hereditary optic neuropathy, bilateral striatal necrosis, coronary atherosclerosis risk and neuropathy, ataxia and retinitis pigmentosa (<jats:styled-content style=\"fixed-case\">NARP<\/jats:styled-content>)\/maternally inherited Leigh syndromes. Here, we present a patient with <jats:styled-content style=\"fixed-case\">NARP<\/jats:styled-content> syndrome, in whom a previously undescribed mutation was detected in the <jats:italic><jats:styled-content style=\"fixed-case\">ATP6<\/jats:styled-content><\/jats:italic> gene: m.<jats:styled-content style=\"fixed-case\">8839G<\/jats:styled-content>&gt;C. Several observations support the concept that m.<jats:styled-content style=\"fixed-case\">8839G<\/jats:styled-content>&gt;C is pathogenically involved in the clinical phenotype of this patient: (1) the mutation was heteroplasmic in muscle; (2) mutation load was higher in the symptomatic patient than in the asymptomatic carriers; (3) cybrids carrying this mutation presented lower cell proliferation, increased mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">mtDNA<\/jats:styled-content>) copy number, increased steady\u2010state <jats:styled-content style=\"fixed-case\">OxPhos<\/jats:styled-content> protein levels and decreased mitochondrial membrane potential with respect to isogenic wild\u2010type cybrids; (4) this change was not observed in 2959 human <jats:styled-content style=\"fixed-case\">mtDNAs<\/jats:styled-content> from different mitochondrial haplogroups; (5) the affected amino acid was conserved in all the <jats:italic><jats:styled-content style=\"fixed-case\">ATP6<\/jats:styled-content><\/jats:italic> sequences analyzed; and (6) using <jats:italic>in silico<\/jats:italic> prediction, the mutation was classified as \u2018probably damaging\u2019. However, measurement of <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> synthesis showed no differences between wild\u2010type and mutated cybrids. Thus, we suggest that m.<jats:styled-content style=\"fixed-case\">8839G<\/jats:styled-content>&gt;C may lower the efficiency between proton translocation within <jats:styled-content style=\"fixed-case\">F<jats:sub>0<\/jats:sub><\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">F<jats:sub>1<\/jats:sub><\/jats:styled-content> rotation, required for <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> synthesis. Further experiments are needed to fully characterize the molecular mechanisms involved in m.<jats:styled-content style=\"fixed-case\">8839G<\/jats:styled-content>&gt;C pathogenicity<\/jats:bold>.<\/jats:p>","DOI":"10.1111\/gbb.12089","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:59:15Z","timestamp":1381543155000},"page":"812-820","source":"Crossref","is-referenced-by-count":24,"title":["Identification and biochemical characterization of the novel mutation m.<scp>8839G<\/scp>&gt;C in the mitochondrial <i><scp>ATP6<\/scp><\/i> gene associated with <scp>NARP<\/scp> syndrome"],"prefix":"10.1111","volume":"12","author":[{"given":"A.","family":"Blanco\u2010Grau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Bonaventura\u2010Ibars","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Coll\u2010Cant\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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