## Protocol Section
### Identification Module
**NCT ID:** NCT03557879

**Acronym:** NGS-NSHL

**Brief Title:** Exome Analysis in Hearing Impaired Patients

**Official Title:** Exome Analysis on Hearing Impaired Patients

#### Organization Study ID Info
**ID:** UF96802
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Montpellier
### Status Module
#### Completion Date
**Date:** 2019-06-01

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** ACTIVE_NOT_RECRUITING
#### Last Update Post Date
**Date:** 2018-06-15

**Type:** ACTUAL

**Last Update Submit Date:** 2018-06-14

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2018-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2018-06-04

**Type:** ACTUAL

**Status Verified Date:** 2018-06

#### Study First Post Date
**Date:** 2018-06-15
**Type:** ACTUAL
**Study First Submit Date:** 2018-06-04
**Study First Submit QC Date:** 2018-06-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Montpellier

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Hearing Impairment

**Keywords:**

- Hearing impairment

- familial

### Design Module

#### Bio Spec

**Description:** Blood samples

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** FAMILY_BASED

**Time Perspective:** RETROSPECTIVE

#### Enrollment Info

**Count:** 30

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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)

**Intervention Names:**

- Genetic: Exome sequencing

**Label:** Hearing impaired families

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Hearing impaired families

**Description:** DNA extracted from samples will undergo exome sequencing, i.e. sequencing of the coding regions of all known human genes (about 22,000)

**Name:** Exome sequencing

**Type:** GENETIC

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**Measure:** identification of candidate genes

**Time Frame:** 1 day

#### Secondary Outcomes

**Description:** Quality assessment of the exome sequencing

**Measure:** Quality assessment of the exome sequencing

**Time Frame:** 1 day

**Description:** Quality assessment of the bioinformatics pipelines used

**Measure:** Quality assessment of the bioinformatics pipelines used

**Time Frame:** 1 day

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 5 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

**Study Population:** Hearing impaired patients and relatives

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Montpellier

**Country:** France

**Facility:** Uhmontpellier

**Zip:** 34295

#### Overall Officials

**Official 1:**

**Affiliation:** University Hospital, Montpellier

**Name:** Anne Françoise ROUX

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006311

- Term: Hearing Disorders

- ID: D000004427

- Term: Ear Diseases

- ID: D000010038

- Term: Otorhinolaryngologic Diseases

- ID: D000012678

- Term: Sensation Disorders

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC09

- Name: Ear, Nose, and Throat Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M24420

- Name: Hearing Loss

- Relevance: HIGH

- As Found: Hearing Impairment

- ID: M6840

- Name: Deafness

- Relevance: HIGH

- As Found: Hearing Impairment

- ID: M9400

- Name: Hearing Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7601

- Name: Ear Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12961

- Name: Otorhinolaryngologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15490

- Name: Sensation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000034381

- Term: Hearing Loss

- ID: D000003638

- Term: Deafness

### Misc Info Module

- Version Holder: 2024-05-24
