Twenty-eight million Americans suffer from hearing impairment. By age 80 about half the population has age related hearing loss (presbycusis). While some degree of presbycusis can be ascribed to environmental exposures a significant fraction is genetically determined. To understand the etiology of age associated hearing impairment it is necessary to understand both the molecular physiology of hearing and the molecular pathology of bearing loss. Identification and characterization of the genes that contribute to the hearing process are required to accomplish this goal. This study proposes to identify and begin to characterize a new gene that causes progressive hearing loss. This autosomal dominant loss begins at high frequencies in the second decade. The chromosomal region containing the gene has been narrowed to approximately 100 cR10,000 at 1 7q25. The DFNA2O chromosomal region will be narrowed by establishing a physical contig across the region and mapping and typing additional polymorphic markers. The DFNA2O causative gene wifi be identified in the narrowed region by evaluating positional candidate genes for cochlear expression and for disease causing mutations. Verification will include sequence analysis of a candidate gene in three affected families. Once identified, the gene will be examined for its potential role in the etiology of presbycusis. The frequency of sequence polymorphisms will be ascertained in the general population and their relationship to presbycusis will be examined in an adult population stratified by age and degree of hearing loss. Postlingual hearing loss genes can be considered potential candidates in the multifactorial causes of presbycusis. DFNA2O an excellent candidate because of its clinical phenotype. Understanding the function of this gene will provide significant insights into the hearing process. Population variations may help to understand its contribution to presbycusis. This knowledge could lead to treatment or prevention of some forms of hearing loss during aging.
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