{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T10:08:37Z","timestamp":1764842917583,"version":"3.41.2"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T00:00:00Z","timestamp":1724198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterozygous mutations in the <jats:italic>OPA3<\/jats:italic> gene are associated with autosomal dominant optic atrophy\u20103 (OPA3), whereas biallelic mutations cause autosomal recessive 3\u2010methylglutaconic aciduria type III. To date, all cases with pathogenic variants in the gene <jats:italic>OPA3<\/jats:italic> have presented with optic atrophy. We report a large family with congenital cataracts, hearing loss and neuropathy, with a likely pathogenic novel missense variant in <jats:italic>OPA3<\/jats:italic>, c.30G&gt;C; p.(Lys10Asn) that segregates with disease in the family pedigree. The family's clinical presentation has significant phenotypic overlap with previously reported cases of OPA3, except for a notable lack of optic atrophy. The analysis of all known disease\u2010associated variants in <jats:italic>OPA3<\/jats:italic> revealed an enrichment in missense variants in patients with OPA3 phenotype compared with loss\u2010of\u2010function variants, which are more likely to be observed in individuals with 3\u2010methylglutaconic aciduria type III, supporting different mechanisms of disease. This case broadens the clinical and genetic spectrum associated with <jats:italic>OPA3<\/jats:italic> mutations and highlights that optic atrophy is not an obligate feature of <jats:italic>OPA3<\/jats:italic>\u2010related disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.63846","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T02:59:53Z","timestamp":1724295593000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel heterozygous <scp><i>OPA3<\/i><\/scp> variant in a family with congenital cataracts, sensorineural hearing loss and neuropathy, without optic atrophy and comparison of pathogenic and population variants"],"prefix":"10.1002","volume":"197","author":[{"given":"Monica","family":"Penon\u2010Portmann","sequence":"first","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"},{"name":"University of Washington  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendyl","family":"Naugle","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"},{"name":"University of California, San Diego  La Jolla California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Brodie","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Schallhorn","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Griggs","sequence":"additional","affiliation":[{"name":"University of Washington  Seattle Washington USA"},{"name":"Northwest Eye Surgeons  Seattle Washington USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"So","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"volume-title":"FBXL4\u2010related encephalomyopathic mitochondrial DNA Depletion syndrome","year":"2017","author":"Almannai M.","key":"e_1_2_9_2_1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/324651"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/CPJ.0000000000000531"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339310"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200975"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm333"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21025"},{"key":"e_1_2_9_9_1","first-page":"373","article-title":"Sur une affection heredo\u2010familiale associant cataracte, atrophie optique, signes extra\u2010pyramidaux et certains stigmates de la maladie de Friedreich. 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