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

NCT ID: NCT04202185

Last Updated: 2026-02-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

150 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-04-02

Study Completion Date

2024-12-06

Brief Summary

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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.

Detailed Description

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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

Conditions

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Congenital Profound Hearing Loss

Study Design

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Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

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G1a

infants under 3 years deaf severe to deep

Data collection

Intervention Type OTHER

Retrospective collection data from diagnostic Data collected following to medical exam as part of care

Genetic analysis

Intervention Type GENETIC

Research of mutation and identification of genetic panel as part of care

G1b

children under 16 years of age with audiologically proven auditory neuropathy

Data collection

Intervention Type OTHER

Retrospective collection data from diagnostic Data collected following to medical exam as part of care

Genetic analysis

Intervention Type GENETIC

Research of mutation and identification of genetic panel as part of care

G2

patients \<25 years old with one or two Otoferlin mutations

Data collection

Intervention Type OTHER

Retrospective collection data from diagnostic Data collected following to medical exam as part of care

Interventions

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Data collection

Retrospective collection data from diagnostic Data collected following to medical exam as part of care

Intervention Type OTHER

Genetic analysis

Research of mutation and identification of genetic panel as part of care

Intervention Type GENETIC

Eligibility Criteria

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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


* 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.


* 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)
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nathalie LOUNDON, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Unité d'Audiophonologie et d'Implantation cochléaire - Necker hospital

Paris, , France

Site Status

Countries

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France

References

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Denoyelle F, Petit C. DFNB9. Adv Otorhinolaryngol. 2002;61:142-4. doi: 10.1159/000066822. No abstract available.

Reference Type BACKGROUND
PMID: 12408076 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16015179 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20230791 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11773575 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12114484 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16226319 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17055430 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16371502 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10192385 (View on PubMed)

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.

Reference Type RESULT
PMID: 40411119 (View on PubMed)

Other Identifiers

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2019-A02968-49

Identifier Type: REGISTRY

Identifier Source: secondary_id

APHP190940

Identifier Type: -

Identifier Source: org_study_id

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