{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T15:57:51Z","timestamp":1785772671075,"version":"3.56.0"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hereditary optic atrophy is characterized by degeneration of retinal ganglion cells and may result from a wide range of genetic etiologies. While pathogenic variants in\n                    <jats:italic>OPA1<\/jats:italic>\n                    and primary mitochondrial variants causing Leber hereditary optic neuropathy (LHON) account for a substantial proportion of cases, many patients remain genetically unsolved. We evaluated the diagnostic yield and clinical impact of comprehensive whole exome\/genome sequencing (WES\/WGS)\u2010based virtual panel testing in 62 partially pre\u2010screened individuals with suspected hereditary optic atrophy. A total of 51 genes associated with optic atrophy and mitochondrial DNA variants were analyzed. Clinical data were systematically retrieved from medical records, including information on extraocular manifestations. A genetic diagnosis was established in 21 patients (33.9%). Pathogenic or likely pathogenic variants in\n                    <jats:italic>OPA1<\/jats:italic>\n                    accounted for 57.1% of solved cases, whereas 42.9% involved other genes, including\n                    <jats:italic>WFS1, ACO2, NR2F1, UCHL1, CACNA1F, and COQ2<\/jats:italic>\n                    . In the majority of patients with non\u2010\n                    <jats:italic>OPA1<\/jats:italic>\n                    findings, the genetic diagnosis prompted additional clinical evaluation, surveillance, or therapeutic intervention. Our findings demonstrate that broad WES\/WGS\u2010based testing increases diagnostic yield and expands the genetic spectrum beyond\n                    <jats:italic>OPA1<\/jats:italic>\n                    and LHON, frequently revealing syndromic conditions with direct clinical implications. Comprehensive genomic testing with broader gene panels should therefore be considered part of the diagnostic workup when hereditary optic atrophy is suspected.\n                  <\/jats:p>","DOI":"10.1111\/cge.70203","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T08:00:07Z","timestamp":1782547207000},"page":"336-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Yield and Clinical Impact of Comprehensive\n                    <scp>WES<\/scp>\n                    \/\n                    <scp>WGS<\/scp>\n                    Testing Beyond Common Genetic Causes in Hereditary Optic Atrophy"],"prefix":"10.1111","volume":"110","author":[{"given":"Katrine M.","family":"Johannesen","sequence":"first","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gr\u00f8nskov","sequence":"additional","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Line","family":"Kessel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Copenhagen University Hospital \u2010 Rigshospitalet  Glostrup Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-6931","authenticated-orcid":false,"given":"Sarah Linea von","family":"Holstein","sequence":"additional","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth Birk","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Kj\u00f8b\u00e6k Gundestrup","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne S\u00f8ndergaard","family":"Khinchi","sequence":"additional","affiliation":[{"name":"Department of Child Neurology Danish Epilepsy Centre  Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Hamann","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Copenhagen University Hospital \u2010 Rigshospitalet  Glostrup Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"},{"name":"Neuro\u2010Ophthalmology Department Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Wegener","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Copenhagen University Hospital \u2010 Rigshospitalet  Glostrup Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Bertelsen","sequence":"additional","affiliation":[{"name":"Department of Genetics Copenhagen University Hospital \u2010 Rigshospitalet  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen 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