Prevalence of POU4F3 and SLC17A8 Mutations

Prevalence of POU4F3 (DFNA15) and SLC17A8 (DFNA25) Genes Mutations in Dominant Autosomal Deafness and Phenotypic Characterization of Carrier Patients.

The study will allow to identify the prevalence of the SLC17A8 gene mutations in patients suffering from deafness. This phenotype also corresponds to DFNA15 deafness caused by POU4F3 : mutations of this gene will be screened as well.

Study Overview

• Status: Terminated
• Conditions: Familial Deafness
• Intervention / Treatment: Genetic: Deafness patients

Detailed Description

DFNA are characterized as progressive bilateral deafness. To date, 21 genes and 57 loci are involved in these dominant deafness, with an unknown prevalence.A 22nd gene responsible of the disease has been found. This SLC17A8 gene encodes for the VGLUT3 protein which is specifically expressed in sensorial cells of the audition. VGlut3-/- mice present a deep deafness due to a deficiency of neurotransmitter release, although sensorial cells and neurons are intact. This kind of deafness is an ideal candidate for a genetic therapy because of the cells integrity.Mutations of SLC17A8 gene have been found in 2 american families that suffer from progressive deafness.The study aims to look for european families from the Mediterranean basin, which carry SLC17A8 gene mutations, and may benefit in a medium-term from genetic therapy. The study will allow to identify the prevalence of the SLC17A8 gene mutations in patients suffering from deafness. This phenotype also corresponds to DFNA15 deafness caused by POU4F3 : mutations of this gene will be screened as well.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34090
    • Mondain Michel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Deafness patients

Description

Inclusion Criteria:

• Age > 18 years

• Patients with a

  1. suggestive neurosensory Deafness: The characteristics of the deafness will be determined from the data of the questionnaire, of the interrogation, the examination and results of the tonal audiometry.

     *Neurosensory deafness: Audiometrics measurement(difference between the tonal audiometric average loss for the frequencies 0,5, 1, 2 and 4 kHz in air conduction and in osseous conduction) < 15 dB for each of both ears.

     • Bilateral symetric: difference between the audiometric thresholds of both ears < or = 15 dB for at least two frequencies.
     • Light to severe: The degree of deafness is defined according to the following classification (moderate hearing loss calculated on the frequencies 500 Hz, 1, 2 and 4 kHz): light hearing deficiency from 20 to 40 dB, moderate hearing deficiency of 40 to 70 dB, severe hearing deficiency of 70 in 90 dB and deep hearing deficiency beyond 90 dB.
     • Whose thresholds frequency by frequency in tonal audiometry (air conduction) are superior to the thresholds of the 90th percentile of the standard ISO 7029.
     • Without environmental exposition factors.

  2. Dominant autosomal transmission diagnosed from one of the following elements:

     • Deafness at a father and his son
     • Deafness at a father and his daughter outside a suggestive context of a dominant form X-related. (deep deafness at the father and light to moderate deafness in daughter)
     • Deafness at a mother and her daughter
     • Deafness at a mother and her son outside a suggestive context of a dominant X-related(light to moderate deafness at the mother, and deep deafness at the son)
     • Deafness at a patient whose a dead parent had a sure or likely deafness according to the criteria of diagnosis mentioned previously
  3. given the consent to participate at this clinical study

Exclusion Criteria:

• Suggestive symptom of a polymalformative syndrom
• familial Consanguinity
• Age < 18 years
• Deafness of transmission or mixed
• Deafness of asymmetric or fluctuating perception
• Prelingual deep Deafness
• Pathology of the ear (otospongiose, disease of Ménière, neurinome of the acoustics)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Deafness patients	Genetic: Deafness patients; SLC17A8 et POU4F3 mutations genes analysis on blood samples of deafness patients.; Other Names: SLC17A8 et POU4F3 mutations genes analysis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLC17A8 et POU4F3 mutations genes analysis	The mutations will be screened by direct sequencing	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phenotypic characterization of the carrier patients	The phenotypic characterization will be assessed by usual tests for genetic deafness (audiometry, electro-physiological explorations)	up to 1 year

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Principal Investigator: Michel MONDAIN, PU-PH, CHRU Montpellier

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): September 1, 2014

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: February 27, 2013
• First Posted (ESTIMATE): March 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): July 21, 2015
• Last Update Submitted That Met QC Criteria: July 20, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Genetic deafness; SLC17A8 et POU4F3 genes
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: 8640; 2010-A00561-38 (OTHER: ID-RCB)