{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T07:51:11Z","timestamp":1774079471576,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health, Labor and Welfare of Japan","award":["H29-Nanchitou(Nan)-Ippan-031"],"award-info":[{"award-number":["H29-Nanchitou(Nan)-Ippan-031"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["20FC10148"],"award-info":[{"award-number":["20FC10148"]}]},{"name":"Ministry of Health, Labor and Welfare of Japan","award":["23FC10149"],"award-info":[{"award-number":["23FC10149"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP16kk0205010"],"award-info":[{"award-number":["JP16kk0205010"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP18ek0109363"],"award-info":[{"award-number":["JP18ek0109363"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP21ek0109542"],"award-info":[{"award-number":["JP21ek0109542"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP24ek0109741"],"award-info":[{"award-number":["JP24ek0109741"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: The OPA1 gene encodes a dynamin-related GTPase essential for mitochondrial fusion. Variants in OPA1 are a major cause of autosomal dominant optic atrophy (DOA). A subset of DOA patients exhibits hearing loss, often manifesting as auditory neuropathy spectrum disorder (ANSD). In this study, we aimed to describe the frequency of OPA1-related hearing loss in a large cohort of patients with hearing loss and to explore the genotype\u2013phenotype correlations and appropriate interventions. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with OPA1 variants were identified. Clinical data, including age of onset, audiological findings, and systemic features, were retrospectively reviewed. Results: Ten individuals from eight independent families carrying OPA1 variants were identified. Three variants were classified as pathogenic or likely pathogenic, while five were variants of uncertain significance. Hearing loss was typically post-lingual in onset and progressive, with predominantly mild-to-moderate severity. Missense variants tended to be associated with DOA-plus phenotypes and ANSD. Five patients obtained only limited benefit from hearing aids, whereas one patient who received a cochlear implant achieved good speech perception. Conclusions: OPA1 is a rare causative gene for hearing loss and is frequently associated with the ANSD phenotype. Affected individuals exhibited phenotypic heterogeneity, which may reflect incomplete penetrance or the influence of mitochondrial DNA-related factors.<\/jats:p>","DOI":"10.3390\/genes17030341","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T11:50:36Z","timestamp":1773921036000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frequency and Hearing Loss Phenotypes of OPA1 Variants in a Cohort of 18,475 Patients with Hearing Impairment"],"prefix":"10.3390","volume":"17","author":[{"given":"Masayuki","family":"Kawakita","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0567-8278","authenticated-orcid":false,"given":"Hideaki","family":"Moteki","sequence":"additional","affiliation":[{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Otolaryngology, Aizawa Hospital, Matsumoto 390-8510, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6640-2297","authenticated-orcid":false,"given":"Shin-ya","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7177-4949","authenticated-orcid":false,"given":"Yumiko","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Iwate Medical University, Morioka 020-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mika","family":"Adachi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Tohoku University Hospital, Sendai 980-8574, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Okano","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Fujita Health University, Toyoake 470-1192, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Shiga University of Medical Science, Otsu 520-2192, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Ohira","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Shonan Kamakura General Hospital, Kamakura 247-8533, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0646-0839","authenticated-orcid":false,"given":"Takashi","family":"Ishino","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Takumi","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-6122","authenticated-orcid":false,"given":"Shin-ichi","family":"Usami","sequence":"additional","affiliation":[{"name":"Department of Hearing Implant Sciences, Shinshu University School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1056\/NEJMra050700","article-title":"Newborn hearing screening\u2014A silent revolution","volume":"354","author":"Morton","year":"2006","journal-title":"N. 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