Exome Analysis in Hearing Impaired Patients (NGS-NSHL)

Exome Analysis on Hearing Impaired Patients

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.

Study Overview

• Status: Unknown
• Conditions: Hearing Impairment
• Intervention / Treatment: Genetic: Exome sequencing

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 Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Uhmontpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Hearing impaired patients and relatives

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hearing impaired families; 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; DNA extracted from samples will undergo exome sequencing, i.e. sequencing of the coding regions of all known human genes (about 22,000)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Study Director: Anne Françoise ROUX, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2018
• Primary Completion (Anticipated): December 31, 2018
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 15, 2018
• Last Update Submitted That Met QC Criteria: June 14, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Hearing impairment; familial
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Otorhinolaryngologic Diseases; Ear Diseases; Sensation Disorders; Hearing Disorders; Hearing Loss; Deafness
• Other Study ID Numbers: UF96802

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No