Hearing impairment is an isolating handicap which seriously compromises the communicative abilities of those affected. Nonsyndromic recessive hearing loss (NSRHL) is a significant cause of congenital sensorineural hearing impairment since about 40% of childhood deafness is due to this etiology. The pathologic mechanisms underlying recessive hearing loss are poorly understood and there is currently no effective prevention or treatment. The exact number of genes involved in NSRHL is unknown but estimates have ranged as high as 120 loci. Such heterogeneity seriously complicates efforts towards their identification. The fact that eight NSRHL genes have already been localized provides a rationale for a well controlled study in a more panmictic population. We propose to establish a resource of NSRHL families for linkage studies and to determine the relative frequencies of the known NSRHL genes. Unlinked USA families, two large NSRHL kindreds, and families from northern Japan and Austria will be subjected to a genome search with an extensive set of marker genes in order to find new linkages. Clinical variation in audiometric profile, onset and progression of hearing loss, vestibular symptoms, and inner ear malformations will be correlated with linkage type to determine if clinical guidelines for diagnosis can be established. Furthermore, families linked to regions containing selected candidate genes will be screened for potential mutations in an attempt to find the specific genes responsible. This project is the first attempt to determine the relapse frequencies of subtypes of NSRHL in any population and as such, will provide new information critical in assessing the public health importance of each subtype. Identification of new hearing loss genes will contribute information necessary for designing new laboratory testing strategies for the diagnosis of NSRHL subtypes. Most importantly, gene localization and identification of hearing impairment genes are the first steps toward the characterization of their expression and function. Better knowledge of the function of these genes will help in directing future research into the most effective means of prevention and treatment.
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