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.

自 20 世纪 90 年代以来，对遗传性听力障碍（主要是在出生时、语前时期或年轻人中检测到的遗传性听力障碍）的研究已经确定了其致病基因。已经发现了导致 140 多种孤立性（非综合征性）耳聋和大约 400 种综合征性耳聋的基因。对这些单基因形式耳聋的小鼠模型的研究为听力的分子机制提供了相当多的见解，特别是那些涉及听觉感觉器官（耳蜗）的发育和/或生理学的机制。与此同时，对这些模型的研究也使得破译听力损伤的病理生理机制成为可能。这促使许多实验室研究基因疗法治疗这些形式的耳聋的潜力。目前已经在小鼠模型中获得了治疗多种耳聋的概念验证，为不久的将来对患者进行耳蜗基因治疗的临床试验铺平了道路。然而，周围性耳聋也可能与中枢听觉功能障碍有关，并且可能远远超出听觉系统本身，这是由于编码的感觉输入改变或因果性耳聋基因参与中枢听觉回路的发育和/或功能所致。 。研究这些中枢功能障碍的多样性、原因和潜在机制，它们可能阻碍外周基因治疗听力恢复的预期益处的方式，并确定如何补救这些问题本身正在成为一个研究领域。在这里，我们概述了有关与遗传性耳聋相关的中心缺陷的当前知识。