{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:05:10Z","timestamp":1771538710614,"version":"3.50.1"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,5,30]],"date-time":"2014-05-30T00:00:00Z","timestamp":1401408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI10\/00662, PI11\/01301"],"award-info":[{"award-number":["PI10\/00662, PI11\/01301"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mutations causing <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>eber hereditary optic neuropathy are usually homoplasmic, show incomplete penetrance, and many of the affected positions are not well conserved through evolution. A large percentage of patients harbouring these mutations have no family history of disease. Moreover, the transfer of the mutation in the cybrid model is frequently not accompanied by the transfer of the cellular, biochemical and molecular phenotype. All these features make difficult their classification as the etiologic factors for this disease. We report a patient who exhibits typical clinical features of <jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>eber hereditary optic neuropathy but lacks all three of the most common mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The diagnosis was made based on clinical studies. The mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> was completely sequenced, and the candidate mutation was analysed in more than 18\u2009000 individuals around the world, its conservation index was estimated in more than 3100 species from protists to mammals, its position was modelled in the crystal structure of a bacteria ortholog subunit, and its functional consequences were studied in a cybrid model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic analysis revealed an m.3472<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>&gt;<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content> transition in the <jats:styled-content style=\"fixed-case\"><jats:italic>M<\/jats:italic><\/jats:styled-content><jats:italic>T\u2010ND1<\/jats:italic> gene that changes a phenylalanine to leucine at position 56. Bioinformatics, molecular\u2010genetic analysis and functional studies suggest that this transition is the etiological factor for the disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This mutation expands the spectrum of deleterious changes in mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>\u2010encoded complex <jats:styled-content style=\"fixed-case\">I<\/jats:styled-content> polypeptides associated with this pathology and highlights the difficulties in assigning pathogenicity to new homoplasmic mutations that show incomplete penetrance in sporadic Leber hereditary optic neuropathy patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ceo.12355","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T09:21:23Z","timestamp":1399454483000},"page":"856-864","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["New 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