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. Over 50 genes associated with autosomal dominant non-syndromic hearing loss (ADNSHL) have been localized and of these, 21 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 emerging. In this competitive renewal, we propose to continue our work localizing and cloning genes that cause ADNSHL. We will also expand the phenotype-genotype studies we have done to facilitate gene identification in small families and continue the RNA interference experiments we initiated to explore novel treatment options for select types of hearing loss.
The specific aims of this proposal are: 1) Specific Aim 1: To continue to localize and clone genes that cause ADNSHL;2) Specific Aim 2: To develop audioprofiling as a method to prioritize genes for mutation screening in families segregating ADNSHL but with an insufficient number of informative meioses for linkage analysis;3) Specific Aim 3: To test the efficacy of RNA interference as a potential therapy in modifying the hearing loss phenotype in a type of ADNSHL caused by a dominant-negative mechanism of action. Completion of these specific aims will not only increase our understanding of the pathogenesis of deafness, but will be highly translational by targeting small families segregating ADNSHL.
|Booth, Kevin T; Azaiez, Hela; Kahrizi, Kimia et al. (2017) Exonic mutations and exon skipping: Lessons learned from DFNA5. Hum Mutat :|
|Korver, Anna M H; Smith, Richard J H; Van Camp, Guy et al. (2017) Congenital hearing loss. Nat Rev Dis Primers 3:16094|
|Matern, Maggie; Vijayakumar, Sarath; Margulies, Zachary et al. (2017) Gfi1Cre mice have early onset progressive hearing loss and induce recombination in numerous inner ear non-hair cells. Sci Rep 7:42079|
|Michel, Vincent; Booth, Kevin T; Patni, Pranav et al. (2017) CIB2, defective in isolated deafness, is key for auditory hair cell mechanotransduction and survival. EMBO Mol Med 9:1711-1731|
|Ortlip, Timothy E; Drake, Virginia E; Raghavan, Prashant et al. (2017) Inflammatory Pseudotumor of the Temporal Bone: A Case Series. Otol Neurotol 38:1024-1031|
|Booth, K T; Kahrizi, K; Babanejad, M et al. (2017) Variants in CIB2 cause DFNB48 and not USH1J. Clin Genet :|
|Shearer, A Eliot; Eppsteiner, Robert W; Frees, Kathy et al. (2017) Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance. Hear Res 348:138-142|
|Shibata, Seiji B; Ranum, Paul T; Moteki, Hideaki et al. (2016) RNA Interference Prevents Autosomal-Dominant Hearing Loss. Am J Hum Genet 98:1101-1113|
|Beheshtian, Maryam; Babanejad, Mojgan; Azaiez, Hela et al. (2016) Heterogeneity of Hereditary Hearing Loss in Iran: a Comprehensive Review. Arch Iran Med 19:720-728|
|Sloan-Heggen, Christina M; Smith, Richard J H (2016) Navigating genetic diagnostics in patients with hearing loss. Curr Opin Pediatr 28:705-712|
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