{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:16:57Z","timestamp":1783016217409,"version":"3.54.6"},"reference-count":8,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004329","name":"The Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P3\u20100108"],"award-info":[{"award-number":["P3\u20100108"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"The Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P3\u20100326"],"award-info":[{"award-number":["P3\u20100326"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"The Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P3\u20100333"],"award-info":[{"award-number":["P3\u20100333"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary optic neuropathies comprise a genetically heterogeneous group of disorders caused by pathogenic variants in mitochondrial and nuclear genes. Despite increasing diagnostic yields, many patients remain without a molecular diagnosis. We report a novel candidate heterozygous variant in the\n                    <jats:italic>PHB1<\/jats:italic>\n                    (Prohibitin 1) gene in a large family affected by autosomal dominant optic atrophy. A three\u2010generation family with slowly progressive visual acuity loss due to optic neuropathy and an apparent autosomal dominant pattern was clinically characterized and recruited for genetic counseling. Exome sequencing and genome\u2010based linkage mapping were performed, alongside protein modeling and in\u00a0vitro experiments to obtain functional evidence. Family\u2010based whole\u2010genome linkage mapping identified a heterozygous missense variant, c.440C&gt;T (p.Ser147Phe), in\n                    <jats:italic>PHB1<\/jats:italic>\n                    in all five affected individuals. The variant substitutes p.Ser147Phe within an evolutionarily conserved alpha\u2010helix domain of PHB1, a mitochondrial protein with multiple roles. In silico modeling suggested that p.Ser147Phe may disrupt PHB1 stability and function through loss of hydrogen bonding, steric hindrance, and altered hydrophobic interactions. In\u00a0vitro experiments suggested potential alterations in mitochondrial dynamics in variant carriers, including a changed ratio of L\u2010OPA1 to S\u2010OPA1 compared with non\u2010carriers. We present initial evidence that\n                    <jats:italic>PHB1<\/jats:italic>\n                    is a novel candidate gene potentially associated with dominant optic atrophy or a related mitochondrial disorder. This represents the first report implicating\n                    <jats:italic>PHB1<\/jats:italic>\n                    in a Mendelian disease. Further studies are required to validate this association.\n                  <\/jats:p>","DOI":"10.1111\/cge.70174","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:40:27Z","timestamp":1777696827000},"page":"165-171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of\n                    <i>PHB1<\/i>\n                    as a Novel Candidate Gene in Dominant Optic Atrophy"],"prefix":"10.1111","volume":"110","author":[{"given":"Marija","family":"Volk","sequence":"first","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9826-0534","authenticated-orcid":false,"given":"Ale\u0161","family":"Maver","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana  Ljubljana Slovenia"},{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina Jarc","family":"Vidmar","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"},{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nu\u0161a","family":"Tro\u0161t","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Vi\u0161njar","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fakin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"},{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Kova\u010d","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"},{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja \u0160u\u0161tar","family":"Habjan","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucija","family":"Malinar","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja Petrovi\u0107","family":"Paji\u0107","sequence":"additional","affiliation":[{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"},{"name":"Clinic for Eye Diseases, University Clinical Centre of Serbia  Belgrade Serbia"},{"name":"Faculty of Medicine University of Belgrade  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ur\u0161ka Dragin","family":"Jerman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Cell Biology, University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rok","family":"Romih","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Institute of Cell Biology, University of Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Hawlina","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"},{"name":"Eye Hospital, University Medical Centre Ljubljana  Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7824-4978","authenticated-orcid":false,"given":"Borut","family":"Peterlin","sequence":"additional","affiliation":[{"name":"Clinical Institute of Genomic Medicine, University Medical Centre Ljubljana  Ljubljana 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