View clinical trials related to DFNA9.
Filter by:To study the positive predictive value of Audiogene v.4.0 open source online machine learning tool in accurately predicting DFNA9 (DeaFNess autosomal dominant ninth) as top 3 gene loci in a large series of genetically confirmed c.151C>T,p.Pro51Ser (p.P51S) variant carriers in COCH (coagulation factor C Homology).
In 2014 radiologic lesions were detected at one or more semicircular canals using CT and MR imaging of temporal bone in subjects carrying the p.P51S mutation in COCH. These lesions are believed to present at more advanced stages of the hearing and vestibular deterioration. Since then, other authors have described similar lesions in advanced non-genetic hearing and vestibular impairment as well. The purpose of this study is therefore to assess the radiologic investigation using CT and MR imaging of temporal bone to all subjects presenting with bilateral vestibulopathy, using the Barany criteria, compared to the p.P51S population.
In 2014 radiological lesions at one or more semicircular canals (SCC) were described using CT & MR imaging in subjects presenting advanced hearing and vestibular deterioration caused by the p.P51S mutation in COCH. Similar lesions were also described in other non-genetic advanced hearing and vestibular deterioration as well. With this prospective observational study it is the purpose to inventory imaging results of candidates for cochlear implantation which are routinely performed during the preoperative work up, since these patient present severe hearing impairment at both ears. A considerable part of them might present vestibular deterioration as well. It is the purpose to detect possible presence of these SCC lesions on CT and MR in this population and the prevalence of these lesions compared to DFNA9 patients.
DFNA9 (Deafness Autosomal Dominant 9) is an autosomal dominant hereditary hearing loss which is associated with vestibular deterioration. The most recent genotype-phenotype correlation studies have been conducted more than 15 years ago. Meanwhile, emerging and valuable vestibular tests have been added to the vestibular test battery. These tests were not available at the time of the correlation studies. The aim of this study is to carry out a prospective cross-sectional study on symptomatic and presymptomatic affected carriers of the Pro51Ser (P51S) Coagulation Factor C Homology (COCH) mutation in order to correlate vestibular data using the complete vestibular test battery with the known data on hearing and vestibular function in relation to age.
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.