Prevalence of POU4F3 and SLC17A8 Mutations

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Familial Deafness

Intervention / Treatment
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* Genetic: Deafness patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Patients with a 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. 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 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Deafness patients<br>Deafness patients | Genetic: Deafness patients<br>* SLC17A8 et POU4F3 mutations genes analysis on blood samples of deafness patients.<br>* Other names: SLC17A8 et POU4F3 mutations genes analysis;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic deafness, SLC17A8 et POU4F3 genes