Hearing impairment is a common sensory deficit with both genetic and environmental etiologies. Large families with hearing loss caused by alterations in a single genetic locus have allowed the isolation and characterization of several genes with diverse functions in the auditory system. Given the complexity of the auditory system, it is not surprising that a broad range of gene products have been implicated in hearing loss. This wealth of genetic heterogeneity provides numerous targets for mutations that may alter auditory abilities and provides an avenue by which novel genes can be discovered or the function of previously cloned genes can be characterized further. However, this heterogeneity also complicates clinical diagnosis. Molecular genetic studies to dissect this complexity will allow clinicians to diagnose precisely the molecular lesion underlying a hearing loss disorder, which should facilitate the most appropriate intervention. Deficits in auditory function at any age can lead to isolation and withdrawal from the hearing population. This proposal introduces two large multigeneration pedigrees with moderate-to-profound, non-syndromic, symmetric, progressive, postlingual sensorineural hearing loss. A genetic linkage and candidate gene approach will be employed to isolate the genes altered in these two families. Characterization of these normal and mutated gene products will contribute further to an understanding of the intricate workings of the auditory system.
