Hearing impairment is a common sensory deficit with both genetic and environmental etiologies. Given the complexity of the auditory system, it is not surprising that a broad range of gene products have been implemented in hearing loss. This wealth of genetic heterogeneity provides numerous targets for mutations that may alter auditory abilities and provides an avenue which novel can discover genes or the function of previously cloned genes can be characterized further. However, this heterogeneity also complicates clinical diagnosis. Molecular genetic studies to dissect this complexity will allow clinicians to diagnose precisely the molecular lesion underlying a hearing loss disorder, which should facilitate the most appropriate intervention. Characterization of modifier genes that may rescue or increase the auditory consequences of a particular mutation in a hearing impaired family may provide predictive value in counseling patients carrying these mutations and genetic variations. Deficits in auditory function at any age can lead to isolation and withdrawal from the hearing population. Therefore it is imperative for hearing researchers to better understand the auditory system and search for mechanisms to curb or cure hearing impairment. A molecular genetic and animal model approach as described in this grant proposal is one path to follow towards accomplishing this task.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC006901-04
Application #
7233590
Study Section
Auditory System Study Section (AUD)
Program Officer
Watson, Bracie
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$287,488
Indirect Cost
Name
University of Washington
Department
Pathology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Kallman, Jeremy C; Phillips, James O; Bramhall, Naomi F et al. (2008) In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier. Otol Neurotol 29:860-7
Street, Valerie A; Kallman, Jeremy C; Strombom, Paul D et al. (2008) Vestibular function in families with inherited autosomal dominant hearing loss. J Vestib Res 18:51-8
Bramhall, Naomi F; Kallman, Jeremy C; Verrall, Aimee M et al. (2008) A novel WFS1 mutation in a family with dominant low frequency sensorineural hearing loss with normal VEMP and EcochG findings. BMC Med Genet 9:48
Street, Valerie A; Kallman, Jeremy C; Robertson, Nahid G et al. (2005) A novel DFNA9 mutation in the vWFA2 domain of COCH alters a conserved cysteine residue and intrachain disulfide bond formation resulting in progressive hearing loss and site-specific vestibular and central oculomotor dysfunction. Am J Med Genet A 139A:86-95