The investigators have studied a large Costa Rican family with autosomal dominant progressive non-syndromic hearing loss (DFNA1), and have recently through positional cloning identified a protein truncation mutation in the human homologue of the Drosophila diaphanous gene. This mutation was found in all deaf family members, and not in normal hearing family members or over 300 control individuals. The goals of this application are (1) to provide functional support for the pathogenicity of this mutation through a) generating mutant mice through homologous recombination and showing that these mouse mutants have a deafness phenotype (specific aims 1 and 3) and b) demonstrating that the protein abnormality leads to abnormal stability or intracellular localization (specific aims 2 and 4), (2) to start the study of proteins interacting with diaphanous which will elucidate the pathogenic pathway and provide candidate genes for other deafness genes (specific aim 5), (3) to study three other deafness families toward the identification of new deafness genes (specific aim 6), and (4) to collect 200 deaf individuals with some family members from the Kaiser Permanente system as a general resource, and screen them for mutations in the diaphanous system (specific aim 7).

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC001076-10
Application #
6174982
Study Section
Hearing Research Study Section (HAR)
Program Officer
Johnson, Thomas E
Project Start
1991-06-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
10
Fiscal Year
2000
Total Cost
$365,688
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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