Systematic Review of Phenotypical Characteristics of P51S COCH Mutation

NCT03707756 | Withdrawn

• 1 other identifier: JessaH-ORL-1
• Study Type: observational
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

DFNA9

Keywords

DFNA9; COCh; Mutation; Genotype-phenotype

Outcome Measures

Primary Outcomes (8)

• age of onset sensorineural hearing loss

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

  10 years

• annual threshold deterioration

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

  10 years

• age of onset vestibular dysfunction

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

  10 years

• annual vestibular deterioration rate

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

  10 years

• Pure Tone Average (PTA)

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

  10 years

• Age-Related Typical Audiogram (ARTA)

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

  10 years

• Time Constant 'T'

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

  10 years

• gain of caloric test of ENG

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

  10 years

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

all affected subjects carrying the P51S COCH mutation

You may qualify if:

• P51S carriership

You may not qualify if:

• no P51S carriership

Sponsors & Collaborators

• Jessa Hospital: lead

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: principal investigator

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 16, 2018
• Study Start: May 1, 2018
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: October 17, 2018

Record last verified: 2018-10