Genetic Study of OTOF- Related Auditory Neuropathy Spectrum Disorder

NCT07778641 | Not Yet Recruiting DMC

• 1 other identifier: Soh-Med-26-8-18MS
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this observational study is to determine the prevalence of OTOF gene variants among patients with auditory neuropathy spectrum disorder (ANSD). The primary research question is whether patients with ANSD carry a pathogenic or likely pathogenic OTOF gene variant. Participants will undergo genetic analysis of the OTOF gene.

Conditions

Auditory Neuropathy Spectrum Disorder; Auditory Neuropathy

Keywords

Otoferlin; Auditory neuropathy spectrum disorder; ANSD; Auditory synaptopathy; Genetic Testing; Whole Exome Sequencing; OTOF mutation; Hereditary hearing loss; Molecular testing; OTOF; OTOF Variants

Outcome Measures

Primary Outcomes (1)

• Study OTOF gene variants among patients with non-syndromic auditory neuropathy spectrum disorder

  At baseline, following enrollment and confirmation of eligibility.

Study Arms (1)

Patients with auditory neuropathy spectrum disorder

Diagnostic Test: Whole exome sequencing.

Interventions

Whole exome sequencing. DIAGNOSTIC_TEST

Whole exome sequencing (WES) will be performed on a biological sample obtained from each eligible participant to analyze the protein-coding regions of the genome. The analysis will specifically assess the OTOF gene for genetic variants associated with auditory neuropathy spectrum disorder (ANSD), while other clinically relevant variants identified through the sequencing may also be documented according to the study protocol. Identified OTOF variants will be classified according to established variant-interpretation criteria.

Patients with auditory neuropathy spectrum disorder

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of patients diagnosed with auditory neuropathy spectrum disorder (ANSD) who meet the predefined eligibility criteria and attend the participating audiology/otolaryngology clinic during the study recruitment period. Eligible participants will undergo genetic analysis to assess for pathogenic or potentially pathogenic variants in the OTOF gene. Participants may include children and adults with ANSD, regardless of sex.

You may qualify if:

• The study will be including 30 subjects of 30 patients of both sexes of any age with congenital hearing loss and confirmed diagnosis of non-syndromic ANSD:
• A) Disproportionate speech discrimination score (SDS) with the hearing threshold level.
• B)The auditory brainstem response (ABR) test with no waveform, disturbed waves, nor detectable wave V at high intense stimulus.
• C) The otoacoustic emission (OAE) and/or cochlear microphonic (CM) potential may be present.
• Informed consent.

You may not qualify if:

• \) Known acquired risk factors of ANSD as preterm, hypoxia, hyperbilirubinemia. 2) Conductive hearing loss. 3) Syndromic ANSD hearing loss. 3) Binaural cochlear implants. 4) Inner ear malformation, cochlear nerve aplasia or hypoplasia.

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Faculty of medicine, Sohag University

Sohag, Sohag Governorate, 82511, Egypt

Location

Related Publications (17)

• Zhang QJ, Han B, Lan L, Zong L, Shi W, Wang HY, Xie LY, Wang H, Zhao C, Zhang C, Yin ZF, Wang DY, Petit C, Guan J, Wang QJ. High frequency of OTOF mutations in Chinese infants with congenital auditory neuropathy spectrum disorder. Clin Genet. 2016 Sep;90(3):238-46. doi: 10.1111/cge.12744. Epub 2016 Mar 11.

  PMID: 26818607 RESULT

• Yong N, Cao M, Anderson E, Downie L, Rance G, Bai J, Liddle K, Howard A, Smith L, Sung V, Wang J. The Genetic Causes of Auditory Neuropathy: A Systematic Review. J Clin Med. 2026 May 31;15(11):4260. doi: 10.3390/jcm15114260.

  PMID: 42279121 RESULT

• Vignesh SS, Jaya V, Muraleedharan A. Prevalence and Audiological Characteristics of Auditory Neuropathy Spectrum Disorder in Pediatric Population: A Retrospective Study. Indian J Otolaryngol Head Neck Surg. 2016 Jun;68(2):196-201. doi: 10.1007/s12070-014-0759-6. Epub 2014 Aug 12.

  PMID: 27340636 RESULT

• Valayannopoulos V, Bance M, Carvalho DS, Greinwald JH Jr, Harvey SA, Ishiyama A, Landry EC, Lowenheim H, Lustig LR, Manrique M, Nash R, Polo R, Pritchett CV, Rubinstein JT, Shearer AE, Del Castillo I, Anderson JJ, Corrales CE, Quigley TM, Riggs WJ, Weber P, Wilson G, Irvin SC, Hassan HE, Chen Y, Liu R, Drummond MC, Sabin LR, Musser BJ, Yancopoulos GD, Kyratsous CA, Herman GA, Baras A, Whitton JP; CHORD Study Group. DB-OTO Gene Therapy for Inherited Deafness. N Engl J Med. 2026 Mar 12;394(11):1074-1083. doi: 10.1056/NEJMoa2400521. Epub 2025 Oct 12.

  PMID: 41085057 RESULT

• Thorpe RK, Azaiez H, Wu P, Wang Q, Xu L, Dai P, Yang T, Schaefer GB, Peters BR, Chan KH, Schatz KS, Bodurtha J, Robin NH, Hirsch Y, Rahbeeni ZA, Yuan H, Smith RJH. The natural history of OTOF-related auditory neuropathy spectrum disorders: a multicenter study. Hum Genet. 2022 Apr;141(3-4):853-863. doi: 10.1007/s00439-021-02340-w. Epub 2021 Aug 23.

  PMID: 34424407 RESULT

• Strenzke N, Chakrabarti R, Al-Moyed H, Muller A, Hoch G, Pangrsic T, Yamanbaeva G, Lenz C, Pan KT, Auge E, Geiss-Friedlander R, Urlaub H, Brose N, Wichmann C, Reisinger E. Hair cell synaptic dysfunction, auditory fatigue and thermal sensitivity in otoferlin Ile515Thr mutants. EMBO J. 2016 Dec 1;35(23):2519-2535. doi: 10.15252/embj.201694564. Epub 2016 Oct 11.

  PMID: 27729456 RESULT

• Shearer AE, Hansen MR. Auditory synaptopathy, auditory neuropathy, and cochlear implantation. Laryngoscope Investig Otolaryngol. 2019 Jul 1;4(4):429-440. doi: 10.1002/lio2.288. eCollection 2019 Aug.

  PMID: 31453354 RESULT

• Sanyelbhaa Talaat H, Kabel AH, Samy H, Elbadry M. Prevalence of auditory neuropathy (AN) among infants and young children with severe to profound hearing loss. Int J Pediatr Otorhinolaryngol. 2009 Jul;73(7):937-9. doi: 10.1016/j.ijporl.2009.03.009. Epub 2009 May 5.

  PMID: 19409623 RESULT

• Santarelli R, Scimemi P, Costantini M, Dominguez-Ruiz M, Rodriguez-Ballesteros M, Del Castillo I. Cochlear Synaptopathy due to Mutations in OTOF Gene May Result in Stable Mild Hearing Loss and Severe Impairment of Speech Perception. Ear Hear. 2021 Nov-Dec 01;42(6):1627-1639. doi: 10.1097/AUD.0000000000001052.

  PMID: 33908410 RESULT

• Saidia AR, Ruel J, Bahloul A, Chaix B, Venail F, Wang J. Current Advances in Gene Therapies of Genetic Auditory Neuropathy Spectrum Disorder. J Clin Med. 2023 Jan 17;12(3):738. doi: 10.3390/jcm12030738.

  PMID: 36769387 RESULT

• Michalski N, Goutman JD, Auclair SM, Boutet de Monvel J, Tertrais M, Emptoz A, Parrin A, Nouaille S, Guillon M, Sachse M, Ciric D, Bahloul A, Hardelin JP, Sutton RB, Avan P, Krishnakumar SS, Rothman JE, Dulon D, Safieddine S, Petit C. Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses. Elife. 2017 Nov 7;6:e31013. doi: 10.7554/eLife.31013.

  PMID: 29111973 RESULT

• Kitao K, Mutai H, Namba K, Morimoto N, Nakano A, Arimoto Y, Sugiuchi T, Masuda S, Okamoto Y, Morita N, Sakamoto H, Shintani T, Fukuda S, Kaga K, Matsunaga T. Deterioration in Distortion Product Otoacoustic Emissions in Auditory Neuropathy Patients With Distinct Clinical and Genetic Backgrounds. Ear Hear. 2019 Jan/Feb;40(1):184-191. doi: 10.1097/AUD.0000000000000586.

  PMID: 29688962 RESULT

• Kim BJ, Jang JH, Han JH, Park HR, Oh DY, Lee S, Kim MY, Kim AR, Lee C, Kim NKD, Park WY, Choung YH, Choi BY. Mutational and phenotypic spectrum of OTOF-related auditory neuropathy in Koreans: eliciting reciprocal interaction between bench and clinics. J Transl Med. 2018 Nov 27;16(1):330. doi: 10.1186/s12967-018-1708-z.

  PMID: 30482216 RESULT

• Hams N, Padmanarayana M, Qiu W, Johnson CP. Otoferlin is a multivalent calcium-sensitive scaffold linking SNAREs and calcium channels. Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):8023-8028. doi: 10.1073/pnas.1703240114. Epub 2017 Jul 10.

  PMID: 28696301 RESULT

• Berlin CI, Morlet T, Hood LJ. Auditory neuropathy/dyssynchrony: its diagnosis and management. Pediatr Clin North Am. 2003 Apr;50(2):331-40, vii-viii. doi: 10.1016/s0031-3955(03)00031-2.

  PMID: 12809326 RESULT

• Bielecki I, Horbulewicz A, Wolan T. Prevalence and risk factors for auditory neuropathy spectrum disorder in a screened newborn population at risk for hearing loss. Int J Pediatr Otorhinolaryngol. 2012 Nov;76(11):1668-70. doi: 10.1016/j.ijporl.2012.08.001. Epub 2012 Aug 29.

  PMID: 22939890 RESULT

• Ford CL, Riggs WJ, Quigley T, Keifer OP Jr, Whitton JP, Valayannopoulos V. The natural history, clinical outcomes, and genotype-phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review. Hum Genet. 2023 Oct;142(10):1429-1449. doi: 10.1007/s00439-023-02595-5. Epub 2023 Sep 7.

  PMID: 37679651 RESULT

MeSH Terms

Conditions

Auditory neuropathy; Deafness, Autosomal Recessive 9; Hearing Loss, Hidden

Interventions

Exome

Condition Hierarchy (Ancestors)

Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Genome; Genetic Structures; Genetic Phenomena

Central Study Contacts

Mira Ayman Ramzy

CONTACT

+201273979650; mira_ayman99@yahoo.com

Mostafa Ahmed Aly Youssif, Professor

CONTACT

+201001313395

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Audio-vestibular medicine resident doctor

Study Record Dates

• First Submitted: August 18, 2026
• First Posted: August 21, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 21, 2026

Record last verified: 2026-08

Locations

EG (1)