Central auditory deficits associated with genetic forms of peripheral deafness

Abstract

Since the 1990s, the study of inherited hearing disorders, mostly those detected at birth, in the prelingual period or in young adults, has led to the identification of their causal genes. The genes responsible for more than 140 isolated (non-syndromic) and about 400 syndromic forms of deafness have already been discovered. Studies of mouse models of these monogenic forms of deafness have provided considerable insight into the molecular mechanisms of hearing, particularly those involved in the development and/or physiology of the auditory sensory organ, the cochlea. In parallel, studies of these models have also made it possible to decipher the pathophysiological mechanisms underlying hearing impairment. This has led a number of laboratories to investigate the potential of gene therapy for curing these forms of deafness. Proof-of-concept has now been obtained for the treatment of several forms of deafness in mouse models, paving the way for clinical trials of cochlear gene therapy in patients in the near future. Nevertheless, peripheral deafness may also be associated with central auditory dysfunctions and may extend well beyond the auditory system itself, as a consequence of alterations to the encoded sensory inputs or involvement of the causal deafness genes in the development and/or functioning of central auditory circuits. Investigating the diversity, causes and underlying mechanisms of these central dysfunctions, the ways in which they could impede the expected benefits of hearing restoration by peripheral gene therapy, and determining how these problems could be remedied is becoming a research field in its own right. Here, we provide an overview of the current knowledge about the central deficits associated with genetic forms of deafness.

Natural History of KCNQ4p.G285S Related Hearing Loss, Construction of iPSC and Mouse Model

“…In the auditory system, KCNQ4 is mainly expressed in hair cells, type I vestibular hair cells, and some auditory pathway neurons 1,11–13 . DPOAE were not evoked at any frequency in either ear of the proband, which is consistent with the pathological lesion caused by the KCNQ4 mutation.…”

Effect of Serious Gaming on Speech-in-Noise Intelligibility in Adult Cochlear Implantees: A Randomized Controlled Study

“…However, taken together, these cognitive abilities explain less than 10% of the inter-individual variability. A more recent review underlined the relationship between profound deafness of genetic origin and the occurrence of central auditory processing disorders in mice [ 42 ]. This is in full agreement with the fact that for a given degree of hearing loss, supraliminal auditory performance may considerably vary from one subject to another.…”

The congenital hearing phenotype in GJB2 in Queensland, Australia: V37I and mild hearing loss predominates

“…Worldwide, GJB2 pathogenic variants account for 18%-50% of prelingual NSHL. [8] In addition, GJB2 variants account for 30-50% of all cases of profound NSHL [9]. Widespread testing of GJB2 (and GJB6), reveals variable degrees of hearing loss (mild to profound), not always detectable at birth, which is usually bilateral, but occasionally unilateral, and can be progressive [3,8].…”