Yasunaga, S. et al. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat. Genet. 21, 363–369 (1999).
Lv, J. et al. AAV1-hOTOF gene therapy for autosomal recessive deafness 9: a single-arm trial. Lancet 403, 2317–2325 (2024).
Wang, H. et al. Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results. Nat. Med. 30, 1898–1904 (2024).
Cheng, X. et al. Gene therapy vs cochlear implantation in restoring hearing function and speech perception for individuals with congenital deafness. JAMA Neurol. 82, 941–951 (2025).
Qi, J. et al. AAV gene therapy for autosomal recessive deafness 9: a single-arm trial. Nat. Med. 31, 2917–2926 (2025).
Morton, C. C. & Nance, W. E. Newborn hearing screening—a silent revolution. N. Engl. J. Med. 354, 2151–2164 (2006).
Lieu, J. E. C., Kenna, M., Anne, S. & Davidson, L. Hearing loss in children: a review. JAMA 324, 2195–2205 (2020).
Sloan-Heggen, C. M. et al. Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Hum. Genet. 135, 441–450 (2016).
Rodríguez-Ballesteros, M. et al. A multicenter study on the prevalence and spectrum of mutations in the otoferlin gene (OTOF) in subjects with nonsyndromic hearing impairment and auditory neuropathy. Hum. Mutat. 29, 823–831 (2008).
Iwasa, Y. I. et al. OTOF mutation analysis with massively parallel DNA sequencing in 2,265 Japanese sensorineural hearing loss patients. PLoS ONE 14, e0215932 (2019).
Choi, B. Y. et al. Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan. Clin. Genet. 75, 237–243 (2009).
Akil, O. et al. Dual AAV-mediated gene therapy restores hearing in a DFNB9 mouse model. Proc. Natl Acad. Sci. USA 116, 4496–4501 (2019).
Zhang, Q. J. et al. High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder. Clin. Genet. 90, 238–246 (2016).
Roux, I. et al. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell 127, 277–289 (2006).
Zhang, L. et al. Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates. Mol. Ther. Methods Clin. Dev. 31, 101154 (2023).
Reisinger, E. & Trapani, I. Gene therapy proves successful in treating hereditary deafness. Lancet 403, 2267–2269 (2024).
Necula, V. et al. Vertigo associated with otosclerosis and stapes surgery—a narrative review. Medicina 59, 1485 (2023).
Quatre, R., Eklöf, M., Wales, J. & Bonnard, Å Long-term hearing outcomes following cochlear implantation in far advanced otosclerosis. Otolaryngol. Head Neck Surg. 172, 2065–2071 (2025).
Terry, B., Kelt, R. E. & Jeyakumar, A. Delayed complications after cochlear implantation. JAMA Otolaryngol. Head Neck Surg. 141, 1012–1017 (2015).
Keithley, E. M. Pathology and mechanisms of cochlear aging. J. Neurosci. Res. 98, 1674–1684 (2020).
Ford, C. L. et al. The natural history, clinical outcomes, and genotype–phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review. Hum. Genet. 142, 1429–1449 (2023).
Paping, D. E. et al. Distortion product otoacoustic emissions in screening for early stages of high-frequency hearing loss in adolescents. Noise Health 24, 20–26 (2022).
Goutman, J. D., Elgoyhen, A. B. & Gomez-Casati, M. E. Cochlear hair cells: the sound-sensing machines. FEBS Lett. 589, 3354–3361 (2015).
Farinetti, A., Raji, A., Wu, H., Wanna, B. & Vincent, C. International consensus (ICON) on audiological assessment of hearing loss in children. Eur. Ann. Otorhinolaryngol. Head Neck Dis. 135, S41–S48 (2018).
Maddox, R. K. & Lee, A. K. C. Auditory brainstem responses to continuous natural speech in human listeners. eNeuro https://doi.org/10.1523/ENEURO.0441-17.2018 (2018).
Gransier, R., Hofmann, M., van Wieringen, A. & Wouters, J. Stimulus-evoked phase-locked activity along the human auditory pathway strongly varies across individuals. Sci. Rep. 11, 143 (2021).
Abdala, C. & Visser-Dumont, L. Distortion product otoacoustic emissions: a tool for hearing assessment and scientific study. Volta Rev. 103, 281–302 (2001).
World Health Organization. World Report on Hearing (World Health Organization, 2021).
Robbins, A. M., Renshaw, J. J. & Berry, S. W. Evaluating meaningful auditory integration in profoundly hearing-impaired children. Am. J. Otol. 12, 144–150 (1991).
Robbins, A. M. & Osberger, M. J. Meaningful Use of Speech Scale (MUSS) (Indiana University School of Medicine, 1990).
Pennini, P. T. M. & Almeida, K. Speech, Spatial and Qualities of Hearing Scale in assessing the benefit in hearing aid users. Codas 33, e20190196 (2021).
Galvin, K. L. & Noble, W. Adaptation of the speech, spatial, and qualities of hearing scale for use with children, parents, and teachers. Cochlear Implants Int. 14, 135–141 (2013).
Archbold, S., Lutman, M. E. & Nikolopoulos, T. Categories of auditory performance: inter-user reliability. Br. J. Audiol. 32, 7–12 (1998).
McDaniel, D. M. & Cox, R. M. Evaluation of the Speech Intelligibility Rating (SIR) test for hearing aid comparisons. J. Speech Hear. Res. 35, 686–693 (1992).
Fu, Q. J., Zhu, M. & Wang, X. Development and validation of the Mandarin speech perception test. J. Acoust. Soc. Am. 129, EL267-273 (2011).
Cheng, X. et al. Music training can improve music and speech perception in pediatric Mandarin-speaking cochlear implant users. Trends Hear. 22, 2331216518759214 (2018).