Prevalence of POU4F3 (DFNA15) and SLC17A8 (DFNA25) Genes Mutations in Dominant Autosomal Deafness and Phenotypic Characterization of Carrier Patients.
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- SLC17A8 et POU4F3 mutations genes analysis
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
排除标准
- •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)
结局指标
主要结局
SLC17A8 et POU4F3 mutations genes analysis
时间窗: up to 1 year
The mutations will be screened by direct sequencing
次要结局
- Phenotypic characterization of the carrier patients(up to 1 year)