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

NCT04202185 | Completed

• 2 other identifiers: APHP1909402019-A02968-49
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Congenital Profound Hearing Loss

Keywords

Auditory neuropathy; DFNB9; Children; Hearing loss; Deafness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

• Audiological characteristics in free fields at diagnosis

  1 day

• Audiological characteristics in separate ears at diagnosis

  1 day

• Audiological characteristics in free fields at 12 months or last record

  12 months

• Audiological characteristics in separate ears at 12 months or last record

  12 months

• Electrophysiological characteristics : auditory evoked potentials (PEA) at diagnosis

  1 day

Study Arms (3)

G1a

infants under 3 years deaf severe to deep

Other: Data collection; Genetic: Genetic analysis

G1b

children under 16 years of age with audiologically proven auditory neuropathy

Other: Data collection; Genetic: Genetic analysis

G2

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

Other: Data collection

Interventions

Data collection OTHER

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

G1a; G1b; G2

Genetic analysis GENETIC

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

G1a; G1b

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

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

Paris, 75015, France

Location

Related Publications (10)

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

  PMID: 12408076 BACKGROUND

• 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.

  PMID: 16015179 BACKGROUND

• 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.

  PMID: 20230791 BACKGROUND

• 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.

  PMID: 11773575 BACKGROUND

• 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.

  PMID: 12114484 BACKGROUND

• 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.

  PMID: 16226319 BACKGROUND

• 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.

  PMID: 17055430 BACKGROUND

• 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.

  PMID: 16371502 BACKGROUND

• 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.

  PMID: 10192385 BACKGROUND

• 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.

  PMID: 40411119 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Serum

MeSH Terms

Conditions

Auditory neuropathy; Hearing Loss; Deafness

Interventions

Data Collection; Genetic Testing

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Nathalie LOUNDON, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2019
• First Posted: December 17, 2019
• Study Start: April 2, 2020
• Primary Completion: October 22, 2023
• Study Completion: December 6, 2024
• Last Updated: February 13, 2026

Record last verified: 2026-02

Locations

FR (1)