The goal of this research is to identify and characterize genes that, when mutated, cause hereditary hearing impairment. Genetic hearing loss accounts for at least half of the cases of hearing loss in the United States. Little is known about the molecular mechanisms of hearing loss. Thus identifying genes and defining how mutations in these genes cause hearing loss will help elucidate the developmental, biological, and physiological processes of hearing. DFNA6 is a gene mapped in a family with dominant, progressive, low- frequency, nonsyndromic sensorineural hearing loss. A second family with similar hearing loss was found to map to a locus (DFNA14) in close proximity to DFNA6. We will narrow the DFNA6 candidate region and determine if it overlaps with the DNA14 region. Novel cDNAs and ESTs will be identified in the candidate region, and candidate genes, including FGFR3, the fibroblast receptor 3 gene, will be tested for mutations. These studies will also include analysis of a second family with dominant nonsyndromic hereditary hearing impairment. Affected individuals in this family develop high frequency, delayed-onset progressive sensorineural hearing loss. Clinical data and DNA samples have been collected from 87 family members of this family to date. Linkage to known dominant deafness loci will be tested, and if ruled out, the samples will be submitted to the Mammalian Genotyping Service for a genome search. Analysis of the genotyping data and fine mapping will be completed by the candidate. The candidate is an academic pediatric otolaryngologist with two and one-half years of previous full-time research experience. The long-term goal of these studies is to improve diagnostic and therapeutic methods for patients with hearing loss. Strong institutional support is available at the University of Michigan in terms of core facilities for research, the sponsor and co-sponsor, and collaborators in hearing research, molecular biology, and molecular genetics.
