Exome Analysis in Hearing Impaired Patients

Study Overview
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Brief Summary
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Hearing impairment is the most frequent sensory deficit in humans and affects one newborn out of 500. The prevalence rises to 3,5/1000 in teenagers due to retarded forms. Most of hearing impairments (about two thirds) have a genetic origin, with recessive, dominant or X-linked mode of inheritance. Some rare forms can be linked to mitochondrial DNA. Molecular diagnosis (i.e. defining the molecular basis of the disease, genes and precise DNA variants) is essential for the follow-up of patients and families. The project intends to perform exome sequencing on 30 samples of families presenting with hearing impairment. Families have been included based on the genetic origin of the hearing impairment (familial cases) and the exclusion of the involvement of 74 known deafness genes. Exome sequencing (sequencing of the coding regions of all known genes, about 22,000) in these cases may underly new gene/disease relationships.

Detailed Description
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Exome sequencing will be performed of 10 trios that each include two affected and one non affected members of a family. Filtering of variants will be performed based on frequency. For each trio, data will be analysed in parallel to follow segregation of the variant(s) in candidate genes. The selected candidate genes will be further characterized in order to ascertain their involvement in hearing function. Finally, once these new genes are well defined as deafness genes , their screening will be added to existing diagnostic panels.

Official Title
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Exome Analysis on Hearing Impaired Patients

Conditions
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Hearing Impairment

Intervention / Treatment
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* Genetic: Exome sequencing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Families presenting with familial hearing impairment, underlying the genetic basis, for whom 74 deafness genes have already been excluded (no evidence of pathogenic genotype) Exclusion criteria: - sporadic cases of hearing impairment, or resolved familial cases

Ages Eligible for Study
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Minimum Age: 5 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 |
| --- | --- |
| Hearing impaired families<br>Samples from families presenting with familial hearing impairment, underlying the genetic basis, for whom 74 deafness genes have already been excluded (no evidence of pathogenic genotype) | Genetic: Exome sequencing<br>* DNA extracted from samples will undergo exome sequencing, i.e. sequencing of the coding regions of all known human genes (about 22,000)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| identification of candidate genes | Description: a candidate gene would present a genotype (combination of DNA variants) compatible with the transmission mode and several lines of evidence of the pathogenic effect of the DNA variants | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality assessment of the exome sequencing | Quality assessment of the exome sequencing | 1 day | 
| Quality assessment of the bioinformatics pipelines used | Quality assessment of the bioinformatics pipelines used | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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familial, Hearing impairment