Evaluation of a Cohort of Congenital Deep Deafness Patients and/or With Auditory Neuropathy, Looking for DFNB9 (AUDIOFERLINE)

Evaluation of a cohort of deaf children looking for autosomal recessive deafness-9 (DFNB9).

Clinical and audiologic evaluation of patients with known auditive neuropathy / auditory dys-synchrony (ANAD) or recently diagnosed congenital severe to profound hearing loss (HL), and assessing genetic analysis looking for DFNB9. The investigators expect to compile genotypic and phenotypic characterization of 25 children with DFNB9 within 4 years.

Study Overview

• Status: Completed
• Conditions: Congenital Profound Hearing Loss
• Intervention / Treatment: Other: Data collection; Genetic: Genetic analysis

Detailed Description

ANAD is not a rare type of hearing loss. Nevertheless, its profile is heterogeneous and the pathology remain underdiagnosed. The investigators will screen all new patients with bilateral severe to profound HL, looking for DFNB9. They will analyse their electrophysiology (auditory potential, and otoacoustic emission), and their audio-vestibular profile, at an early stage and one year after inclusion. All patients will be seen in the genetic clinic. Also, the investigators will analyse all patients with ANAD profile and patients known with ANAD.

All informations will provide precise data base to allow a better understanding of the pathology. It might also lead to select the best candidates for future gene therapy

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• France
  • Paris, France, 75015
    • Unité d'Audiophonologie et d'Implantation cochléaire - Necker hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 25 years (Child, Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patient coming to the Necker Hospital for a deafness visit or for a check-up prior to a cochlear implantation

Description

G1a / Inclusion Criteria:

• Child from 0 to 3 years old
• Child with severe to profound bilateral deafness newly diagnosed with:
• Average hearing threshold> 70 decibel on each ear
• and / or no response to 70 decibel PEA on each ear
• and / or no response to ASSR

G1b / Inclusion Criteria:

• Child under 16
• Child with newly diagnosed hearing neuropathy : tonal/vocal dissociation (when this is possible), and/or modified PEA, and/or discordant ASSR, and/or OEA present.

G2 / Inclusion Criteria:

• Adult patient under 25 or child
• Patient with deafness with auditory neuropathy
• Patient known to have 1 or 2 mutations of the otoferlin protein

Exclusion Criteria:

• Other type of deafness such as : unilateral deafness, deafness of transmission, malformation syndrome, known genetic familial deafness not DFNB9
• Patient without medical insurance
• Lack of consent to DNA sampling, of one or both biological parents (consent of the care)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
G1a; infants under 3 years deaf severe to deep	Other: Data collection; Retrospective collection data from diagnostic Data collected following to medical exam as part of care; Genetic: Genetic analysis; Research of mutation and identification of genetic panel as part of care
G1b; children under 16 years of age with audiologically proven auditory neuropathy	Other: Data collection; Retrospective collection data from diagnostic Data collected following to medical exam as part of care; Genetic: Genetic analysis; Research of mutation and identification of genetic panel as part of care
G2; patients <25 years old with one or two Otoferlin mutations	Other: Data collection; Retrospective collection data from diagnostic Data collected following to medical exam as part of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of deafness caused by DFNB9	Prevalence and type of bi-allelic pathogenic changes Otoferlin Molecular analysis will be done by Next Generation Sequencing Capture method	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Audiological characteristics in free fields at diagnosis	audiometric thresholds on 500, 1000, 2000, 4000 Hz in free fields	1 day
Audiological characteristics in separate ears at diagnosis	audiometric thresholds on 500, 1000, 2000, 4000 Hz in separate ears	1 day
Audiological characteristics in free fields at 12 months or last record	audiometric thresholds on 500, 1000, 2000, 4000 Hz in free fields	12 months
Audiological characteristics in separate ears at 12 months or last record	audiometric thresholds on 500, 1000, 2000, 4000 Hz in separate ears	12 months
Electrophysiological characteristics : auditory evoked potentials (PEA) at diagnosis	PEA thresholds per ear	1 day
Electrophysiological characteristics : auditory evoked potentials (PEA) at 12 months or last record	PEA thresholds per ear	12 months
Electrophysiological characteristics : auditory Steady State Response (ASSR) at diagnosis	ASSR thresholds per ear at 500, 1000, 2000, 4000 Hz	1 day
Electrophysiological characteristics : auditory Steady State Response (ASSR) at 12 months or last record	ASSR thresholds per ear at 500, 1000, 2000, 4000 Hz	12 months
Electrophysiological characteristics : otoacoustic emissions (OEAs) at diagnosis	OEAs status	1 day
Electrophysiological characteristics : otoacoustic emissions (OEAs) at 12 months or last record	OEAs status	12 months
Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at diagnosis	PEOM	1 day
Vestibular characteristics : per-oral endoscopic myotomy (PEOM) at 12 months or last record	PEOM	12 months
Vestibular characteristics : video Head Impulse Test (VHIT) at diagnosis	VHIT	1 day
Vestibular characteristics : video Head Impulse Test (VHIT) at 12 months or last record	VHIT	12 months
Caloric Tests at diagnosis	Caloric Tests	1 day
Caloric Tests at 12 months or last record	Caloric Tests	12 months
Clinical development scale at diagnosis	For child under 3 years with : walk age, sitting age and head held age	1 day
Clinical development scale at 12 months or last record	For child under 3 years with : walk age, sitting age and head held age	12 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin
• Investigators: Principal Investigator: Nathalie LOUNDON, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

General Publications

• Denoyelle F, Petit C. DFNB9. Adv Otorhinolaryngol. 2002;61:142-4. doi: 10.1159/000066822. No abstract available.
• Loundon N, Marcolla A, Roux I, Rouillon I, Denoyelle F, Feldmann D, Marlin S, Garabedian EN. Auditory neuropathy or endocochlear hearing loss? Otol Neurotol. 2005 Jul;26(4):748-54. doi: 10.1097/01.mao.0000169044.63970.4a.
• Marlin S, Feldmann D, Nguyen Y, Rouillon I, Loundon N, Jonard L, Bonnet C, Couderc R, Garabedian EN, Petit C, Denoyelle F. Temperature-sensitive auditory neuropathy associated with an otoferlin mutation: Deafening fever! Biochem Biophys Res Commun. 2010 Apr 9;394(3):737-42. doi: 10.1016/j.bbrc.2010.03.062. Epub 2010 Mar 16.
• Mehl AL, Thomson V. The Colorado newborn hearing screening project, 1992-1999: on the threshold of effective population-based universal newborn hearing screening. Pediatrics. 2002 Jan;109(1):E7. doi: 10.1542/peds.109.1.e7.
• Migliosi V, Modamio-Hoybjor S, Moreno-Pelayo MA, Rodriguez-Ballesteros M, Villamar M, Telleria D, Menendez I, Moreno F, Del Castillo I. Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss. J Med Genet. 2002 Jul;39(7):502-6. doi: 10.1136/jmg.39.7.502. No abstract available.
• Rouillon I, Marcolla A, Roux I, Marlin S, Feldmann D, Couderc R, Jonard L, Petit C, Denoyelle F, Garabedian EN, Loundon N. Results of cochlear implantation in two children with mutations in the OTOF gene. Int J Pediatr Otorhinolaryngol. 2006 Apr;70(4):689-96. doi: 10.1016/j.ijporl.2005.09.006. Epub 2005 Oct 13.
• Roux I, Safieddine S, Nouvian R, Grati M, Simmler MC, Bahloul A, Perfettini I, Le Gall M, Rostaing P, Hamard G, Triller A, Avan P, Moser T, Petit C. Otoferlin, defective in a human deafness form, is essential for exocytosis at the auditory ribbon synapse. Cell. 2006 Oct 20;127(2):277-89. doi: 10.1016/j.cell.2006.08.040.
• Varga R, Avenarius MR, Kelley PM, Keats BJ, Berlin CI, Hood LJ, Morlet TG, Brashears SM, Starr A, Cohn ES, Smith RJ, Kimberling WJ. OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. J Med Genet. 2006 Jul;43(7):576-81. doi: 10.1136/jmg.2005.038612. Epub 2005 Dec 21.
• Yasunaga S, Grati M, Cohen-Salmon M, El-Amraoui A, Mustapha M, Salem N, El-Zir E, Loiselet J, Petit C. A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness. Nat Genet. 1999 Apr;21(4):363-9. doi: 10.1038/7693.
• Bouazza N, Semeraro M, Lui G, Froelicher-Bournaud L, Choupeaux L, Treluyer JM, Benaboud S, Terzic J, Hachulla E, Remy P, Harambat J, Karras A, Rousset-Rouviere C, Jolivot A, Amoura Z, Daugas E, Hummel A, Salomon R, Lega JC, Decramer S, Belot A, Gobert D, Costedoat-Chalumeau N, Faguer S, Melki I, Jourde-Chiche N, Bader-Meunier B. Population pharmacokinetic modelling of prednisolone in systemic lupus erythematosus patients: Analysis of exposure and disease activity. Br J Clin Pharmacol. 2025 Oct;91(10):2854-2864. doi: 10.1002/bcp.70103. Epub 2025 May 23.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2020
• Primary Completion (Actual): October 22, 2023
• Study Completion (Actual): December 6, 2024

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: December 16, 2019
• First Posted (Actual): December 17, 2019

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Children; Hearing loss; Deafness; Auditory neuropathy; DFNB9
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hearing Loss; Deafness; Auditory neuropathy; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Genetic Techniques; Genetic Services; Diagnostic Services; Genetic Testing; Data Collection
• Other Study ID Numbers: APHP190940; 2019-A02968-49 (Registry Identifier: ID-RCB)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No