Exome Analysis in Hearing Impaired Patients

• Conditions: Hearing Impairment
• Interventions: Genetic: Exome sequencing

• Registration Number: NCT03557879
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

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

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.

Study Timeline

• Status Verified: 2018-06
• Study Start: 2018-06-04
• Study First Submitted: 2018-06-04
• Study First Submitted QC: 2018-06-14
• Last Update Submitted: 2018-06-14
• Study First Posted: 2018-06-15
• Last Update Posted: 2018-06-15
• Primary Completion: 2018-12-31
• Study Completion: 2019-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Hearing impaired families	Exome sequencing	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)

Primary Outcome Measures

Name	Time	Method
identification of candidate genes	1 day	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

Secondary Outcome Measures

Name	Time	Method
Quality assessment of the exome sequencing	1 day	Quality assessment of the exome sequencing
Quality assessment of the bioinformatics pipelines used	1 day	Quality assessment of the bioinformatics pipelines used

Trial Locations

Locations (1)

Uhmontpellier; 🇫🇷 Montpellier, France