The goal of this proposal is to identify molecular basis of non-syndromic deafness by using a multidisciplinary Approach in several unique resources of patients/families from Far Eastern populations. We have a large and expanding collection of genomic DNA from patients/families with non-syndromic deafness from China and Japan First, because of genetic heterogeneity, large multigenerational families and consanguineous families have been selected for study that are independently capable of yielding evidence of for linkage. We will then seek to identify and ultimately clone the relevant genes by the positional candidate gene approach. Second, a novel sequential screening strategy will be used to identify new genes for deafness in probands from multiplex families. Candidate genes to be screened will include the human orthologs of murine genes for deafness and other members of gene families in which some are known to be the cause of deafness. The research will yield important information o ethnic differences in the frequency and distribution of mutations at currently recognized genes for non-syndromic deafness. Using available information on outcome variables such as age of onset, audiologic findings, and the mating structure of the deaf population, these data will permit a search for clinically relevant genotype-phenotype correlations and a clearer understanding of the cause for secular changes in the frequency of specific forms o genetic deafness. Finally, we will use yeast 2-hybrid systems and the immunoaffinity chromatography to search for proteins that interact with the products of the MYO7A and USH1C genes. The identification of such interactions could lead to identifying potential modifiers and exciting new therapeutic approaches to attenuate the specific effects of mutations on the cochlear. The proposed work will identify the new gene (s) for non-syndromic deafness and enable us to understand better cellular and molecular basis of genetic deafness. Our studies will develop a more comprehensive picture of the involvement of genes in non-syndromic deafness to gain further insight into the function of these genes in the inner ear. This knowledge is an essential prerequisite to the development and provision of molecular diagnostic services for families with non-syndromic deafness.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005575-02
Application #
6523683
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Watson, Bracie
Project Start
2001-09-15
Project End
2006-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
2
Fiscal Year
2002
Total Cost
$254,181
Indirect Cost
Name
University of Miami School of Medicine
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
Mittal, Rahul; Bencie, Nicole; Parrish, James M et al. (2018) An Update on Phosphodiesterase Mutations Underlying Genetic Etiology of Hearing Loss and Retinitis Pigmentosa. Front Genet 9:9
Mittal, Rahul; Patel, Amit P; Nguyen, Desiree et al. (2018) Genetic basis of hearing loss in Spanish, Hispanic and Latino populations. Gene 647:297-305
Wang, Li; Yan, Denise; Qin, Litao et al. (2018) Amino acid 118 in the Deafness Causing (DFNA20/26) ACTG1 gene is a Mutational Hot Spot. Gene Rep 11:264-269
Snapp, Hillary A; Hoffer, Michael E; Liu, Xuezhong et al. (2017) Effectiveness in Rehabilitation of Current Wireless CROS Technology in Experienced Bone-Anchored Implant Users. Otol Neurotol 38:1397-1404
Li, Jia-Nan; Chen, Si; Zhai, Lei et al. (2017) The Advances in Hearing Rehabilitation and Cochlear Implants in China. Ear Hear 38:647-652
Mittal, Rahul; Nguyen, Desiree; Patel, Amit P et al. (2017) Recent Advancements in the Regeneration of Auditory Hair Cells and Hearing Restoration. Front Mol Neurosci 10:236
Mittal, Rahul; Grati, M'hamed; Sedlacek, Miloslav et al. (2016) Characterization of ATPase Activity of P2RX2 Cation Channel. Front Physiol 7:186
Ma, Q; Grati, M; Bai, F et al. (2016) Rescue from early-onset hearing loss in a mouse model lacking the cyclin-dependent kinase inhibitor p19Ink4d. Cell Death Dis 7:e2131
Tekin, Demet; Yan, Denise; Bademci, Guney et al. (2016) A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes. Hear Res 333:179-184
Knecht, Leslie D; O'Connor, Gregory; Mittal, Rahul et al. (2016) Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host. EBioMedicine 9:161-169

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