Mitochondrial deafness.

Hearing impairment is a common disorder, largely genetic in origin, and showing classical features of a heterogeneous genetic disease. Up to 100 independently acting nuclear genes are involved in the disorder, of which around 30 have been mapped, but only a handful identified. Mutations in mitochondrial DNA also play a significant role in both syndromic and nonsyndromic sensorineural hearing impairment. Environmental agents such as aminoglycoside antibiotics and as yet unidentified nuclear genes interact with mitochondrial mutations in the expression of auditory phenotypes. The spectrum of different mitochondrial mutations associated with hearing impairment, taken together with mechanistic studies at the molecular level, suggests that the pathogenic process involves the accumulation of abnormal translation products inside mitochondria, in sensitive cells of the auditory system. This leads to a prediction of the involvement of a novel class of nuclear genes in hearing impairment, namely those with roles in 'mitochondrial protein quality control'.