The relative contribution of heredity to age-related hearing loss is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic (Van Camp et aL, 1997). Over 40 genes associated with autosomal dominant non-syndromic hearing loss have been localized and of these, 15 have been cloned. Although the function of many of these genes in the inner ear is unclear, an understanding of the biology of hearing and deafness at a molecular level is beginning to emerge.In this competitive renewal, we propose to continue our work localizing and cloning genes that cause autosomal dominant non-syndromic hearing loss. In addition, we will initiate functional studies on two of the genes we cloned during the past granting period.
The specific aims of this proposal are:(1) To localize and clone additional genes for autosomal dominant non-syndromic hearing loss;(2) To study the cellular and molecular mechanisms underlying inner ear defects in mice with targeted mutations of Eya4;(3) To study tectorial membrane micromechanics in a mouse mutant with a targeted deletion of Coil 1a2 (Coil la2-/-and a second mutant that recapitulates the DFNA1 3 genotype (Coil 1a2 Arg549Cys);(4) To offer genetic counseling to select families with autosomal dominant non-syndromic hearing loss
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