{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:42:20Z","timestamp":1760708540035,"version":"build-2065373602"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2509800","2023YFC2508400"],"award-info":[{"award-number":["2023YFC2509800","2023YFC2508400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100016073","name":"Key Technologies Research and Development Program of Anhui Province","doi-asserted-by":"publisher","award":["2023YFF1203504"],"award-info":[{"award-number":["2023YFF1203504"]}],"id":[{"id":"10.13039\/100016073","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82222016","82271171"],"award-info":[{"award-number":["82222016","82271171"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Auditory neuropathy (AN) represents a clinical manifestation of <jats:italic>OPA1<\/jats:italic>-related diseases. The diagnostic process of these diseases is challenging owing to the broad spectrum of intermediate phenotypes and diverse inherited patterns. The aim of this study was to comprehensively delineate the feature of <jats:italic>OPA1<\/jats:italic>-related patients in a Chinese AN cohort, encompassing the incident rate, inherited pattern, detailed audiological characteristics, and genotype-phenotype correlation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Between 2003 and 2020, 452 unrelated probands with a diagnosis of AN were referred to our laboratory for molecular genetic investigation with high-throughput sequencing. Sanger sequencing was performed on the probands and their parents to verify the genetic results. Patients diagnosed as AN by clinical evaluation, auditory brainstem responses, otoacoustic emission and\/or cochlear microphonic. Comprehensive auditory evaluations were conducted on <jats:italic>OPA1<\/jats:italic>-related patients, and some of them were performed a follow-up study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We identified seven probands (1.55%, 7\/452) with <jats:italic>OPA1<\/jats:italic> variants in seven unrelated families, demonstrating distinct genetic patterns, including one family with rare autosomal recessive (AR) inheritance, six families with autosomal dominant (AD) inheritance (three were AD de novo). The AN phenotype was observed in all patients prior to the second decade of life, with AN serving as the initial presenting symptom in two patients. Additionally, probands with the rare AR inheritance exhibited a more severe phenotype. A total of eight <jats:italic>OPA1<\/jats:italic> variants were identified, including a novel variant c.2013\u2009+\u20095G\u2009&gt;\u2009C. The GTPase domain of <jats:italic>OPA1<\/jats:italic> exclusively harbored missense variants, and 85.71% (6\/7) of the patients carried one of missense variants in <jats:italic>OPA1<\/jats:italic>. The observed phenotypes exhibited a broad spectrum of manifestations, encompassing vestibular dysfunction and developmental delay, with varying degrees of hearing loss. Among the seven patients, four exhibited severe to profound hearing loss. The annual rates of hearing loss at the frequencies of speech were 2.74 dB\/year for one patient, who underwent a 10-year-old follow-up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our results indicated the distinct genetic patterns and variable phenotypic characteristics of <jats:italic>OPA1<\/jats:italic>-related AN in the Chinese population. The audiological features of <jats:italic>OPA1<\/jats:italic>-related patients were comprehensively described as exhibiting AN. We identified one novel splicing variants that expand the genetic spectrum of <jats:italic>OPA1<\/jats:italic> variants in AN.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13023-025-04040-4","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T12:26:07Z","timestamp":1760703967000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinct genetic patterns and natural history of OPA1-related auditory neuropathy in Chinese population"],"prefix":"10.1186","volume":"20","author":[{"given":"Hongyang","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linyi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fen","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"issue":"3","key":"4040_CR1","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/nrneurol.2016.10","volume":"12","author":"T Moser","year":"2016","unstructured":"Moser T, Starr A. Auditory neuropathy\u2013neural and synaptic mechanisms. Nat Reviews Neurol. 2016;12(3):135\u201349.","journal-title":"Nat Reviews Neurol"},{"issue":"Pt 11","key":"4040_CR2","doi-asserted-by":"publisher","first-page":"3141","DOI":"10.1093\/brain\/awv270","volume":"138","author":"G Rance","year":"2015","unstructured":"Rance G, Starr A. Pathophysiological mechanisms and functional hearing consequences of auditory neuropathy. Brain. 2015;138(Pt 11):3141\u201358.","journal-title":"Brain"},{"issue":"03","key":"4040_CR3","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1055\/s-2002-34456","volume":"23","author":"YS Sininger","year":"2002","unstructured":"Sininger YS. Identification of auditory neuropathy in infants and children. Semin Hear. 2002;23(03):193\u2013200.","journal-title":"Semin Hear"},{"issue":"2","key":"4040_CR4","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ijporl.2010.11.023","volume":"75","author":"VKC Manchaiah","year":"2011","unstructured":"Manchaiah VKC, Zhao F, Danesh AA, Duprey R. The genetic basis of auditory neuropathy spectrum disorder (ANSD). Int J Pediatr Otorhinolaryngol. 2011;75(2):151\u20138.","journal-title":"Int J Pediatr Otorhinolaryngol"},{"issue":"6","key":"4040_CR5","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1002\/ana.20681","volume":"58","author":"P Amati-Bonneau","year":"2005","unstructured":"Amati-Bonneau P, Guichet A, Olichon A, Chevrollier A, Viala F, Miot S, Ayuso C, Odent S, Arrouet C, Verny C, et al. OPA1 R445H mutation in optic atrophy associated with sensorineural deafness. Ann Neurol. 2005;58(6):958\u201363.","journal-title":"Ann Neurol"},{"issue":"2","key":"4040_CR6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41580-024-00785-1","volume":"26","author":"L-C T\u00e1bara","year":"2025","unstructured":"T\u00e1bara L-C, Segawa M, Prudent J. Molecular mechanisms of mitochondrial dynamics. Nat Rev Mol Cell Biol. 2025;26(2):123\u201346.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"4040_CR7","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.ymgme.2011.04.018","volume":"103","author":"CP Schaaf","year":"2011","unstructured":"Schaaf CP, Blazo M, Lewis RA, Tonini RE, Takei H, Wang J, Wong L-J, Scaglia F. Early-onset severe neuromuscular phenotype associated with compound heterozygosity for OPA1 mutations. Mol Genet Metab. 2011;103(4):383\u20137.","journal-title":"Mol Genet Metab"},{"issue":"Pt 4","key":"4040_CR8","doi-asserted-by":"publisher","first-page":"e169","DOI":"10.1093\/brain\/awq306","volume":"134","author":"C Marelli","year":"2011","unstructured":"Marelli C, Amati-Bonneau P, Reynier P, Layet V, Layet A, Stevanin G, Brissaud E, Bonneau D, Durr A, Brice A. Heterozygous OPA1 mutations in behr syndrome. Brain. 2011;134(Pt 4):e169. author reply e170.","journal-title":"Brain"},{"issue":"Pt 10","key":"4040_CR9","doi-asserted-by":"publisher","first-page":"e301","DOI":"10.1093\/brain\/awu184","volume":"137","author":"D Bonneau","year":"2014","unstructured":"Bonneau D, Colin E, Oca F, Ferr\u00e9 M, Chevrollier A, Gu\u00e9guen N, Desquiret-Dumas V, N\u2019Guyen S, Barth M, Zanlonghi X, et al. Early-onset behr syndrome due to compound heterozygous mutations in OPA1. Brain. 2014;137(Pt 10):e301.","journal-title":"Brain"},{"issue":"Pt 1","key":"4040_CR10","doi-asserted-by":"publisher","first-page":"e321","DOI":"10.1093\/brain\/awu234","volume":"138","author":"V Carelli","year":"2015","unstructured":"Carelli V, Sabatelli M, Carrozzo R, Rizza T, Schimpf S, Wissinger B, Zanna C, Rugolo M, La Morgia C, Caporali L, et al. Behr syndrome\u2019 with OPA1 compound heterozygote mutations. Brain. 2015;138(Pt 1):e321.","journal-title":"Brain"},{"key":"4040_CR11","doi-asserted-by":"crossref","unstructured":"Othman BA, Ong JE, Dumitrescu AV. Biallelic optic atrophy 1 (OPA1) related disorder-case report and literature review. Genes (Basel). 2022;13(6).","DOI":"10.3390\/genes13061005"},{"issue":"Pt 3","key":"4040_CR12","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1093\/brain\/awq007","volume":"133","author":"P Yu-Wai-Man","year":"2010","unstructured":"Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, et al. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010;133(Pt 3):771\u201386.","journal-title":"Brain"},{"issue":"Pt 7","key":"4040_CR13","doi-asserted-by":"publisher","first-page":"e236","DOI":"10.1093\/brain\/aws340","volume":"136","author":"S Leruez","year":"2013","unstructured":"Leruez S, Milea D, Defoort-Dhellemmes S, Colin E, Crochet M, Procaccio V, Ferr\u00e9 M, Lamblin J, Drouin V, Vincent-Delorme C, et al. Sensorineural hearing loss in OPA1-linked disorders. Brain. 2013;136(Pt 7):e236.","journal-title":"Brain"},{"issue":"4","key":"4040_CR14","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1097\/MAO.0000000000000978","volume":"37","author":"K Namba","year":"2016","unstructured":"Namba K, Mutai H, Takiguchi Y, Yagi H, Okuyama T, Oba S, Yamagishi R, Kaneko H, Shintani T, Kaga K, et al. Molecular impairment mechanisms of novel OPA1 mutations predicted by molecular modeling in patients with autosomal dominant optic atrophy and auditory neuropathy spectrum disorder. Otology Neurotology: Official Publication Am Otological Soc Am Neurotology Soc [and] Eur Acad Otology Neurotology. 2016;37(4):394\u2013402.","journal-title":"Otology Neurotology: Official Publication Am Otological Soc Am Neurotology Soc [and] Eur Acad Otology Neurotology"},{"key":"4040_CR15","first-page":"559","volume":"25","author":"A Maeda-Katahira","year":"2019","unstructured":"Maeda-Katahira A, Nakamura N, Hayashi T, Katagiri S, Shimizu S, Ohde H, Matsunaga T, Kaga K, Nakano T, Kameya S, et al. Autosomal dominant optic atrophy with OPA1 gene mutations accompanied by auditory neuropathy and other systemic complications in a Japanese cohort. Mol Vis. 2019;25:559\u201373.","journal-title":"Mol Vis"},{"issue":"1","key":"4040_CR16","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/humu.20607","volume":"29","author":"S Schimpf","year":"2008","unstructured":"Schimpf S, Fuhrmann N, Schaich S, Wissinger B. Comprehensive cDNA study and quantitative transcript analysis of mutant OPA1 transcripts containing premature termination codons. Hum Mutat. 2008;29(1):106\u201312.","journal-title":"Hum Mutat"},{"key":"4040_CR17","doi-asserted-by":"crossref","unstructured":"Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, et al. Bilateral visual improvement with unilateral gene therapy injection for leber hereditary optic neuropathy. Sci Transl Med. 2020;12(573).","DOI":"10.1126\/scitranslmed.aaz7423"},{"issue":"Pt 3","key":"4040_CR18","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1093\/brain\/awu378","volume":"138","author":"R Santarelli","year":"2015","unstructured":"Santarelli R, Rossi R, Scimemi P, Cama E, Valentino ML, La Morgia C, Caporali L, Liguori R, Magnavita V, Monteleone A, et al. OPA1-related auditory neuropathy: site of lesion and outcome of cochlear implantation. Brain. 2015;138(Pt 3):563\u201376.","journal-title":"Brain"},{"key":"4040_CR19","unstructured":"Diagnosis CM-CRCGoC, Neuropathy IoA, Head EBoCJoO, Surgery N, Head SoO, Neck Surgery CMA, Audiology So, Vestibular Medicine CIE, Medical PAf, Care H. Chinese Clinical Practice Guidelines for Auditory Neuropathy (gCAN). World J Otorhinolaryngol Head Neck Surg. n\/a(n\/a)."},{"issue":"4","key":"4040_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/mgg3.394","volume":"6","author":"H Wang","year":"2018","unstructured":"Wang H, Wu K, Guan J, Yang J, Xie L, Xiong F, Lan L, Wang D, Wang Q. Identification of four TMC1 variations in different Chinese families with hereditary hearing loss. Mol Genet Genomic Med. 2018;6(4):504\u201313.","journal-title":"Mol Genet Genomic Med"},{"issue":"11","key":"4040_CR21","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1002\/humu.23630","volume":"39","author":"AM Oza","year":"2018","unstructured":"Oza AM, DiStefano MT, Hemphill SE, Cushman BJ, Grant AR, Siegert RK, Shen J, Chapin A, Boczek NJ, Schimmenti LA, et al. Expert specification of the ACMG\/AMP variant interpretation guidelines for genetic hearing loss. Hum Mutat. 2018;39(11):1593\u2013613.","journal-title":"Hum Mutat"},{"issue":"D1","key":"4040_CR22","doi-asserted-by":"publisher","first-page":"D948","DOI":"10.1093\/nar\/gkae1071","volume":"53","author":"SC Dyer","year":"2025","unstructured":"Dyer SC, Austine-Orimoloye O, Azov AG, Barba M, Barnes I, Barrera-Enriquez VP, Becker A, Bennett R, Beracochea M, Berry A, et al. Ensembl 2025. Nucleic Acids Res. 2025;53(D1):D948\u201357.","journal-title":"Nucleic Acids Res"},{"issue":"10","key":"4040_CR23","doi-asserted-by":"publisher","first-page":"104311","DOI":"10.1016\/j.ejmg.2021.104311","volume":"64","author":"J Guan","year":"2021","unstructured":"Guan J, Li J, Chen G, Shi T, Lan L, Wu X, Zhao C, Wang D, Wang H, Wang Q. Family trio-based sequencing in 404 sporadic bilateral hearing loss patients discovers recessive and de Novo genetic variants in multiple ways. Eur J Med Genet. 2021;64(10):104311.","journal-title":"Eur J Med Genet"},{"issue":"3","key":"4040_CR24","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s00439-024-02652-7","volume":"143","author":"H Wang","year":"2024","unstructured":"Wang H, Guan L, Wu X, Guan J, Li J, Li N, Wu K, Gao Y, Bing D, Zhang J, et al. Clinical and genetic architecture of a large cohort with auditory neuropathy. Hum Genet. 2024;143(3):293\u2013309.","journal-title":"Hum Genet"},{"issue":"3","key":"4040_CR25","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/S0161-6420(80)35247-0","volume":"87","author":"CS Hoyt","year":"1980","unstructured":"Hoyt CS. Autosomal dominant optic atrophy. A spectrum of disability. Ophthalmology. 1980;87(3):245\u201351.","journal-title":"Ophthalmology"},{"issue":"10","key":"4040_CR26","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1136\/bjo.2007.134726","volume":"92","author":"AC Cohn","year":"2008","unstructured":"Cohn AC, Toomes C, Hewitt AW, Kearns LS, Inglehearn CF, Craig JE, Mackey DA. The natural history of OPA1-related autosomal dominant optic atrophy. Br J Ophthalmol. 2008;92(10):1333\u20136.","journal-title":"Br J Ophthalmol"},{"issue":"4","key":"4040_CR27","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ajo.2006.12.038","volume":"143","author":"AC Cohn","year":"2007","unstructured":"Cohn AC, Toomes C, Potter C, Towns KV, Hewitt AW, Inglehearn CF, Craig JE, Mackey DA. Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations. Am J Ophthalmol. 2007;143(4):656\u201362.","journal-title":"Am J Ophthalmol"},{"issue":"4","key":"4040_CR28","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1007\/s00438-021-01783-0","volume":"296","author":"X Xu","year":"2021","unstructured":"Xu X, Wang P, Jia X, Sun W, Li S, Xiao X, Hejtmancik JF, Zhang Q. Pathogenicity evaluation and the genotype-phenotype analysis of OPA1 variants. Mol Genet Genomics. 2021;296(4):845\u201362.","journal-title":"Mol Genet Genomics"},{"key":"4040_CR29","doi-asserted-by":"crossref","unstructured":"Thavapalan V, Liang TW, Rakocevic G. Novel OPA1 mutation in syndromic mitochondrial dominant optic atrophy (DOA+): A case report (P7.074). Neurology 2015, 84.","DOI":"10.1212\/WNL.84.14_supplement.P7.074"},{"issue":"10","key":"4040_CR30","doi-asserted-by":"publisher","first-page":"6987","DOI":"10.1167\/iovs.14-14953","volume":"55","author":"J Chen","year":"2014","unstructured":"Chen J, Xu K, Zhang X, Jiang F, Liu L, Dong B, Ren Y, Li Y. Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy. Investig Ophthalmol Vis Sci. 2014;55(10):6987\u201395.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"4040_CR31","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.nbd.2015.08.015","volume":"90","author":"JM de la Chao","year":"2016","unstructured":"de la Chao JM, Prunier-Mirebeau D, Amati-Bonneau P, Ferr\u00e9 M, Sarzi E, Bris C, Leruez S, Chevrollier A, Desquiret-Dumas V, Gueguen N, et al. OPA1-related disorders: diversity of clinical expression, modes of inheritance and pathophysiology. Neurobiol Dis. 2016;90:20\u20136.","journal-title":"Neurobiol Dis"},{"issue":"Pt 8","key":"4040_CR32","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1093\/brain\/awu165","volume":"137","author":"T Bonifert","year":"2014","unstructured":"Bonifert T, Karle KN, Tonagel F, Batra M, Wilhelm C, Theurer Y, Schoenfeld C, Kluba T, Kamenisch Y, Carelli V, et al. Pure and syndromic optic atrophy explained by deep intronic OPA1 mutations and an intralocus modifier. Brain. 2014;137(Pt 8):2164\u201377.","journal-title":"Brain"},{"issue":"1","key":"4040_CR33","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41420-025-02442-8","volume":"11","author":"S-Q Yao","year":"2025","unstructured":"Yao S-Q, Liang J-J, Zhou H, Tan S, Cao Y, Chen C-B, Xu C, Wang R, Li T-P, Zhao F-F, et al. Contrasting pathophysiological mechanisms of OPA1 mutations in autosomal dominant optic atrophy. Cell Death Discov. 2025;11(1):259.","journal-title":"Cell Death Discov"},{"issue":"7","key":"4040_CR34","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1016\/j.ajhg.2023.06.002","volume":"110","author":"LC Walker","year":"2023","unstructured":"Walker LC, Hoya Mdl, Wiggins GAR, Lindy A, Vincent LM, Parsons MT, Canson DM, Bis-Brewer D, Cass A, Tchourbanov A, et al. Using the ACMG\/AMP framework to capture evidence related to predicted and observed impact on splicing: recommendations from the ClinGen SVI splicing subgroup. Am J Hum Genet. 2023;110(7):1046\u201367.","journal-title":"Am J Hum Genet"},{"issue":"13","key":"4040_CR35","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1093\/bioinformatics\/bty960","volume":"35","author":"J Shamsani","year":"2019","unstructured":"Shamsani J, Kazakoff SH, Armean IM, McLaren W, Parsons MT, Thompson BA, O\u2019Mara TA, Hunt SE, Waddell N, Spurdle AB. A plugin for the ensembl variant effect predictor that uses MaxEntScan to predict variant spliceogenicity. Bioinformatics. 2019;35(13):2315\u20137.","journal-title":"Bioinformatics"},{"issue":"10","key":"4040_CR36","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.tem.2022.07.003","volume":"33","author":"J Noone","year":"2022","unstructured":"Noone J, O\u2019Gorman DJ, Kenny HC. OPA1 regulation of mitochondrial dynamics in skeletal and cardiac muscle. Trends Endocrinol Metab. 2022;33(10):710\u201321.","journal-title":"Trends Endocrinol Metab"},{"issue":"7976","key":"4040_CR37","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/s41586-023-06462-1","volume":"620","author":"SB Nyenhuis","year":"2023","unstructured":"Nyenhuis SB, Wu X, Strub M-P, Yim Y-I, Stanton AE, Baena V, Syed ZA, Canagarajah B, Hammer JA, Hinshaw JE. OPA1 helical structures give perspective to mitochondrial dysfunction. Nature. 2023;620(7976):1109\u201316.","journal-title":"Nature"},{"key":"4040_CR38","doi-asserted-by":"crossref","unstructured":"Daumke O, van der Laan M. Molecular machineries shaping the mitochondrial inner membrane. Nat Rev Mol Cell Biol. 2025.","DOI":"10.1038\/s41580-025-00854-z"},{"issue":"1","key":"4040_CR39","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.cell.2006.06.025","volume":"126","author":"C Frezza","year":"2006","unstructured":"Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, et al. OPA1 controls apoptotic Cristae remodeling independently from mitochondrial fusion. Cell. 2006;126(1):177\u201389.","journal-title":"Cell"},{"key":"4040_CR40","doi-asserted-by":"crossref","unstructured":"Liang FG, Zandkarimi F, Lee J, Axelrod JL, Pekson R, Yoon Y, Stockwell BR, Kitsis RN. OPA1 promotes ferroptosis by augmenting mitochondrial ROS and suppressing an integrated stress response. Mol Cell. 2024;84(16).","DOI":"10.1016\/j.molcel.2024.07.020"},{"issue":"5","key":"4040_CR41","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s00418-007-0321-7","volume":"128","author":"S Bette","year":"2007","unstructured":"Bette S, Zimmermann U, Wissinger B, Knipper M. OPA1, the disease gene for optic atrophy type Kjer, is expressed in the inner ear. Histochem Cell Biol. 2007;128(5):421\u201330.","journal-title":"Histochem Cell Biol"},{"issue":"1","key":"4040_CR42","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1007\/s00018-024-05115-4","volume":"81","author":"C Affortit","year":"2024","unstructured":"Affortit C, Coyat C, Saidia AR, Ceccato J-C, Charif M, Sarzi E, Flamant F, Guyot R, Cazevieille C, Puel J-L, et al. The human OPA1delTTAG mutation induces adult onset and progressive auditory neuropathy in mice. Cell Mol Life Sci. 2024;81(1):80.","journal-title":"Cell Mol Life Sci"},{"issue":"6","key":"4040_CR43","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1002\/lio2.978","volume":"7","author":"K Wu","year":"2022","unstructured":"Wu K, Lan L, Shi W, Li J, Xie L, Xiong F, Wang H, Wang Q. The audiological characteristics of infant auditory neuropathy patients without otoacoustic emission. Laryngoscope Investig Otolaryngol. 2022;7(6):2095\u2013102.","journal-title":"Laryngoscope Investig Otolaryngol"},{"issue":"Pt 5","key":"4040_CR44","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1093\/brain\/awt056","volume":"136","author":"DP Wynne","year":"2013","unstructured":"Wynne DP, Zeng F-G, Bhatt S, Michalewski HJ, Dimitrijevic A, Starr A. Loudness adaptation accompanying ribbon synapse and auditory nerve disorders. Brain. 2013;136(Pt 5):1626\u201338.","journal-title":"Brain"},{"issue":"4","key":"4040_CR45","doi-asserted-by":"publisher","first-page":"639","DOI":"10.3390\/audiolres11040059","volume":"11","author":"R Santarelli","year":"2021","unstructured":"Santarelli R, Scimemi P, La Morgia C, Cama E, Del Castillo I, Carelli V. Electrocochleography in auditory neuropathy related to mutations in the OTOF or OPA1 gene. Audiol Res. 2021;11(4):639\u201352.","journal-title":"Audiol Res"},{"key":"4040_CR46","doi-asserted-by":"crossref","unstructured":"Huang T, Santarelli R, Starr A. Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals. Brain Res. 2009;1300.","DOI":"10.1016\/j.brainres.2009.08.083"},{"issue":"5","key":"4040_CR47","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1001\/jamaoto.2019.4314","volume":"146","author":"T White-Schwoch","year":"2020","unstructured":"White-Schwoch T, Anderson S, Kraus N. Long-term Follow-up of a patient with auditory neuropathy and normal hearing thresholds. JAMA Otolaryngol Head Neck Surg. 2020;146(5):499\u2013501.","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"issue":"1\u20132","key":"4040_CR48","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jns.2010.03.014","volume":"293","author":"K Mizutari","year":"2010","unstructured":"Mizutari K, Matsunaga T, Inoue Y, Kaneko H, Yagi H, Namba K, Shimizu S, Kaga K, Ogawa K. Vestibular dysfunction in a Japanese patient with a mutation in the gene OPA1. J Neurol Sci. 2010;293(1\u20132):23\u20138.","journal-title":"J Neurol Sci"},{"issue":"1","key":"4040_CR49","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1186\/s40478-019-0740-4","volume":"7","author":"G van Hameren","year":"2019","unstructured":"van Hameren G, Campbell G, Deck M, Berthelot J, Gautier B, Quintana P, Chrast R, Tricaud N. In vivo real-time dynamics of ATP and ROS production in axonal mitochondria show decoupling in mouse models of peripheral neuropathies. Acta Neuropathol Commun. 2019;7(1):86.","journal-title":"Acta Neuropathol Commun"},{"key":"4040_CR50","doi-asserted-by":"publisher","first-page":"5625768","DOI":"10.1155\/2020\/5625768","volume":"2020","author":"H Wang","year":"2020","unstructured":"Wang H, Bing D, Li J, Xie L, Xiong F, Lan L, Wang D, Guan J, Wang Q. High frequency of AIFM1 variants and phenotype progression of auditory neuropathy in a Chinese population. Neural Plast. 2020;2020:5625768.","journal-title":"Neural Plast"},{"issue":"6","key":"4040_CR51","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41419-023-05899-6","volume":"14","author":"Y Qiu","year":"2023","unstructured":"Qiu Y, Wang H, Fan M, Pan H, Guan J, Jiang Y, Jia Z, Wu K, Zhou H, Zhuang Q, et al. Impaired AIF-CHCHD4 interaction and mitochondrial calcium overload contribute to auditory neuropathy spectrum disorder in patient-iPSC-derived neurons with AIFM1 variant. Cell Death Dis. 2023;14(6):375.","journal-title":"Cell Death Dis"},{"key":"4040_CR52","doi-asserted-by":"publisher","first-page":"749484","DOI":"10.3389\/fcell.2021.749484","volume":"9","author":"W Wang","year":"2021","unstructured":"Wang W, Li J, Lan L, Xie L, Xiong F, Guan J, Wang H, Wang Q. Auditory neuropathy as the initial phenotype for patients with ATP1A3 c.2452 G\u2009>\u2009A: Genotype-Phenotype study and CI management. Front Cell Dev Biology. 2021;9:749484.","journal-title":"Front Cell Dev Biology"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04040-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04040-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04040-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:04:14Z","timestamp":1760706254000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-04040-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":52,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4040"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04040-4","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]},"assertion":[{"value":"9 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the Committee of Medical Ethics of Chinese PLA General Hospital (S2020\u2011228\u201101). Written informed consent was obtained from participants. The data pertaining to patients from the Multicenter Study on Clinical Diagnosis and Intervention of Acoustic Neuropathy (registration number: ChiCTR2100050125; date of registration: August 16, 2021; institution hospital: Chinese PLA General Hospital).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The medical records and samples of all patients were used for research purposes with their informed written consent. In the case of underage probands, informed written consent was obtained from their parents or guardians.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors have no other funding, financial relationships, or no conflicts of interest to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"520"}}