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It is most associated with biallelic variants in the\n                      <jats:italic>OTOF<\/jats:italic>\n                      gene. Despite growing genetic insights, its long-term natural history remains poorly characterized, and the functional consequences of specific\n                      <jats:italic>OTOF<\/jats:italic>\n                      variants are incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective case series included 5 Han Chinese patients with TSAN carrying\n                      <jats:italic>OTOF<\/jats:italic>\n                      variants. Comprehensive audiological evaluations, including auditory brainstem response (ABR), otoacoustic emissions (OAE), cochlear microphonics (CM), pure-tone audiometry, and speech recognition assessment, were performed. Genetic analyses included whole-exome sequencing, Sanger validation, in silico pathogenicity prediction, and structural modeling. Long-term clinical follow-up ranged from 5 to 21 years.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All patients initially presented with fluctuating mild-to-profound hearing loss, absent ABR, and preserved OAE and\/or CM, consistent with AN. Genetic analysis identified 7 rare\n                      <jats:italic>OTOF<\/jats:italic>\n                      variants, including 2 frameshift variants (p. Gln994Valfs*7 and p. Leu795Serfs*5), 1 nonsense variant (p. Arg1134Ter), and 4 missense variants (p. Arg1607Trp, p. Gly541Ser, p. Trp536Cys, and p. Ala1667Asp). Most variants affected evolutionarily conserved residues and were predicted to be deleterious, while structural modeling suggested that the missense variants may alter local protein conformation and stability. Long-term follow-up revealed marked inter-individual variability in auditory outcomes. Several patients achieved near-normal auditory performance without intervention, with Categories of Auditory Performance scores of 7 and Speech Intelligibility Rating scores of 5, whereas others showed persistent speech perception deficits despite only moderate hearing thresholds. Cochlear implantation improved auditory performance in one patient.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      <jats:italic>OTOF<\/jats:italic>\n                      -related TSAN demonstrated substantial clinical heterogeneity but generally favorable long-term functional outcomes in this cohort. These findings contribute to the characterization of the\n                      <jats:italic>OTOF<\/jats:italic>\n                      mutational landscape in TSAN, highlight the importance of long-term monitoring in this rare disease, and support individualized management strategies guided by both genotype and functional auditory performance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04500-5","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:26:30Z","timestamp":1784132790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temperature-sensitive auditory neuropathy: long-term follow-up and genotypic correlation"],"prefix":"10.1186","volume":"21","author":[{"given":"Xin","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiujing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-7279","authenticated-orcid":false,"given":"Qiuju","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"4500_CR1","doi-asserted-by":"publisher","unstructured":"Chinese Multi-Center Research Collaborative Group on Clinical Diagnosis and Intervention of Auditory Neuropathy; Editorial Board of Chinese Journal of Otorhinolaryngology Head and Neck Surgery; Society of Otorhinolaryngology Head and Neck Surgery, Chinese Medical Association; Society of Audiology and Vestibular Medicine, China International Exchange and Promotive Association for Medical and Health Care, Wu X-N, Shi T, Li D-Y, Zhang X-L, Song M-T, et al. Chinese Clinical Practice Guidelines for Auditory Neuropathy (gCAN). World J Otorhinolaryngol Head Neck Surg. 2026;12:1\u201324. https:\/\/doi.org\/10.1002\/wjo2.70003.","DOI":"10.1002\/wjo2.70003"},{"issue":"Pt 3","key":"4500_CR2","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/brain\/119.3.741","volume":"119","author":"A Starr","year":"1996","unstructured":"Starr A, Picton TW, Sininger Y, Hood LJ, Berlin CI. Auditory neuropathy. Brain. 1996;119(Pt 3):741\u201353. https:\/\/doi.org\/10.1093\/brain\/119.3.741.","journal-title":"Brain"},{"key":"4500_CR3","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. 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