Hearing loss: Mechanisms revealed by genetics and cell biology

Hearing loss (HL), or deafness in its most severe form, affects an estimated 28 and 22.5 million Americans and Europeans, respectively. The numbers are higher in regions such as India and the Middle East, where consanguinity contributes to larger numbers of recessively inherited hearing impairment (HI). As a result of work-related difficulties, educational and developmental delays, and social stigmas and exclusion, the economic impact of HL is very high. At the other end of the spectrum, a rich deaf culture, particularly for individuals whose parents and even grandparents were deaf, is a social movement that believes that deafness is a difference in human experience rather than a disability. This review attempts to cover the remarkable progress made in the field of the genetics of HL over the past 20 years. Mutations in a significant number of genes have been discovered over the years that contribute to clinically heterogeneous forms of HL, enabling genetic counseling and prediction of progression of HL. Cell biological assays, protein localization in the inner ear, and detailed analysis of spontaneous and transgenic mouse models have provided an incredibly rich resource for elucidating mechanisms of hereditary hearing loss (HHL). This knowledge is providing answers for the families with HL, who contribute a great deal to the research being performed worldwide.