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Report for Clinical Trial NCT03707756

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Systematic Review of Phenotype Characteristics of DFNA9 Caused by the Pro51 Ser (P51S) Mutation in COCH

Gene mutations account for more than 60% of congenital sensorineural hearing loss (SNHL) in Western Countries. Hereditary SNHL does not necessarily start at birth, however, as many causative gene mutations only begin to express at much later ages, such as for example DFNA9, also known as the ninth discovered autosomal dominant SNHL. It is characterized by a late onset of rapid progressive SNHL together with accompanying vestibular impairment. The first reported DFNA9 patients were carrying the c.151 C>T mutation in COCH, which is the result of a substitution of cytosine by thymine nucleotide of the 151th base pair (c.151C>T). At protein level, this missense point mutation induces a mistranslation to a serine instead of a proline amino-acid (p.Pro51Ser, (P51S)), producing mutant cochlin that cause a dominant negative effect due to misfolding. In the perspective of promising future hearing and vestibular treatment developments, such as gene therapy, stem cell therapy, neural regeneration, in association with cochlear and/or vestibular implantation, a more accurate understanding of the onset of the very first signs of the auditory and vestibular deterioration is important. However, in early stages these first signs of impairment are very discrete and pre-symptomatic. The aim of this systematic review is to identify studies related to DFNA9, caused by the P51S COCH variant, describing detailed genotype-phenotype correlation in relation to the age and to investigate the age of onset of the SNHL and peripheral vestibular function as well as their progression in relation to age.

NCT03707756 DFNA9


Primary Outcomes

Description: Age of onset sensorineural hearing loss (years) in P51S COCH mutation carriers

Measure: age of onset sensorineural hearing loss

Time: 10 years

Description: Annual threshold deterioration (decibel hearing loss per year) in P51S COCH mutation carriers

Measure: annual threshold deterioration

Time: 10 years

Description: Age of onset vestibular dysfunction (time constant T (seconds) in P51S COCH mutation carriers

Measure: age of onset vestibular dysfunction

Time: 10 years

Description: Annual vestibular deterioration (seconds per year) in P51S COCH mutation carriers

Measure: annual vestibular deterioration rate

Time: 10 years

Description: Pure tone average (PTA) in decibel hearing loss (dB HL) of P51S COCH mutations carriers

Measure: Pure Tone Average (PTA)

Time: 10 years

Description: Age-related typical audiogram (ARTA) of P51S COCH mutation carriers

Measure: Age-Related Typical Audiogram (ARTA)

Time: 10 years

Description: Time constant 'T' with velocity-step test(VST) (seconds) in P51S COCH mutation carriers

Measure: Time Constant 'T'

Time: 10 years

Description: summation of gain in caloric test of electronystagmography (ENG) (degrees per second) of P51S COCH mutation carriers

Measure: gain of caloric test of ENG

Time: 10 years

Time Perspective: Retrospective

Other


There is one SNP

SNPs


1 P51S

Systematic Review of Phenotype Characteristics of DFNA9 Caused by the Pro51 Ser (P51S) Mutation in COCH. --- P51S ---

Systematic Review of Phenotypical Characteristics of P51S COCH Mutation Gene mutations account for more than 60% of congenital sensorineural hearing loss (SNHL) in Western Countries. --- P51S ---

At protein level, this missense point mutation induces a mistranslation to a serine instead of a proline amino-acid (p.Pro51Ser, (P51S)), producing mutant cochlin that cause a dominant negative effect due to misfolding. --- P51S ---

The aim of this systematic review is to identify studies related to DFNA9, caused by the P51S COCH variant, describing detailed genotype-phenotype correlation in relation to the age and to investigate the age of onset of the SNHL and peripheral vestibular function as well as their progression in relation to age. --- P51S ---

Age of onset sensorineural hearing loss (years) in P51S COCH mutation carriers. --- P51S ---

Annual threshold deterioration (decibel hearing loss per year) in P51S COCH mutation carriers. --- P51S ---

Age of onset vestibular dysfunction (time constant T (seconds) in P51S COCH mutation carriers. --- P51S ---

Annual vestibular deterioration (seconds per year) in P51S COCH mutation carriers. --- P51S ---

Pure tone average (PTA) in decibel hearing loss (dB HL) of P51S COCH mutations carriers. --- P51S ---

Age-related typical audiogram (ARTA) of P51S COCH mutation carriers. --- P51S ---

Time constant 'T' with velocity-step test(VST) (seconds) in P51S COCH mutation carriers. --- P51S ---

summation of gain in caloric test of electronystagmography (ENG) (degrees per second) of P51S COCH mutation carriers. --- P51S ---

Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership DFNA9 The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. --- P51S ---

Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership DFNA9 The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. --- P51S --- --- P51S ---

Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership DFNA9 The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. --- P51S --- --- P51S --- --- P51S ---

Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership DFNA9 The strategy and methodology used for the systematic review was based on the PRISMA Statement (Preferred Reporting Items for Systematic Reviews and Meta-Analysis Medline, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge and Web of Science were searched. --- P51S --- --- P51S --- --- P51S --- --- P51S ---



HPO Nodes