Systematic Review of Phenotypical Characteristics of P51S COCH Mutation

Само регистрирани потребители могат да превеждат статии

Вход / Регистрация

Линкът е запазен в клипборда

Състояние

Спонсори

Jessa Hospital

КЛИНИЧНО ИЗСЛЕДВАНЕ: NCT03707756

BioSeek: NCT03707756

Ключови думи

Резюме

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.

Описание

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. Information was retrieved about COCH mutations causing DFNA9, including phenotype, genotype, audiometric and vestibular data.

Audiometric data were collected using individual measurements or pure tone average incides in the selected records.In case of different audiometric data presentation, for instance audiograms or different pure tone average (PTA) plots against age, a comprehensive assessment and inventory of all individual measurements was conducted. All available measurements at both ears per frequency were inventoried and a binaural mean value for each frequency per age was averaged, before the calculation of the indices. If longitudinal measurements of the same individual were shown, all the available data was included in the assessment.

The following parameters for the audiometric data were inventoried: pure tone average (PTA), Annual Threshold detarioration (ATD) per frequency and/or PTA, Age-related Typical Audiogram (ARTA) and age of onset of the sensorineural hearing loss (SNHL).

For the vestibular function, all different parameters of the vestibular function were inventoried. Normative values, if mentioned, were used to evaluate the measurements. An overall inventory of all individual vestibular measurements in relation to age was conducted.

The following parameters for the vestibular function were inventoried: Time Constant (T) derived from velocity-step test (VST) in seconds, Caloric response gain on electronystagmography, Annual vestibular deterioration rate and age of onset of vestibular dysfunction.

Дати

Последна проверка:	09/30/2018
Първо изпратено:	10/07/2018
Очаквано записване подадено:	10/10/2018
Първо публикувано:	10/15/2018
Изпратена последна актуализация:	10/14/2018
Последна актуализация публикувана:	10/16/2018
Действителна начална дата на проучването:	04/30/2018
Приблизителна дата на първично завършване:	09/29/2018
Очаквана дата на завършване на проучването:	09/29/2018

Състояние или заболяване

DFNA9

Фаза

Критерии за допустимост

Полове, допустими за проучване	All
Метод за вземане на проби	Probability Sample
Приема здрави доброволци	Не
Критерии	Inclusion Criteria: - P51S carriership Exclusion Criteria: - no P51S carriership

Резултат

Първични изходни мерки

1. age of onset sensorineural hearing loss [10 years]

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

2. annual threshold deterioration [10 years]

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

3. age of onset vestibular dysfunction [10 years]

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

4. annual vestibular deterioration rate [10 years]

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

5. Pure Tone Average (PTA) [10 years]

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

6. Age-Related Typical Audiogram (ARTA) [10 years]

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

7. Time Constant 'T' [10 years]

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

8. gain of caloric test of ENG [10 years]

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

Systematic Review of Phenotypical Characteristics of P51S COCH Mutation

Ключови думи

thymine

пролин

cytosine

атрофия

увреждане на слуха