With increasing age, median hearing thresholds insidiously deteriorate to such an extent that late onset, progressive hearing impairment is the most common neurological disability of the elderly. Although hearing loss of at least 25 decibels (dB) is present in only 1% of young adults between 18-24 years of age this figure increases to 10% in individuals between 55-64 years of age and to approximately 50% in octogenarians. The relative contribution of heredity to age-related hearing impairment is not known, however the majority of inherited late-onset hearing loss appears to be autosomal dominant and non-syndromic. In several large families in which this type of impairment is segregating, linkage analysis has been used to localize the relevant genes. To date, thirteen different genes responsible for autosomal dominant non- syndromic hearing loss (ADNSHL) have been localized; only one has been cloned.
The specific aims of this proposal are to localize additional genes from ADNSH in appropriately studied large kindreds; to clone candidate genes for DFNA10 and DFNA13; to demonstrate mutations in these candidate genes; and, to offer genetic counseling to families with DFNA4, DFNA10, and DFNA13. By localizing many of the relevant ADHSHL genes and cloning the more common ones, this research will lead to better understanding of progressive, late-onset hereditary hearing impairment in the United States. This knowledge will foster the development of studies in gene- gene interactions, gene environment interactions, and ultimately, therapeutic intervention to prevent progression of some forms of hearing impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC003544-03
Application #
6175947
Study Section
Hearing Research Study Section (HAR)
Program Officer
Johnson, Thomas E
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$301,873
Indirect Cost
Name
University of Iowa
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Matern, Maggie S; Beirl, Alisha; Ogawa, Yoko et al. (2018) Transcriptomic Profiling of Zebrafish Hair Cells Using RiboTag. Front Cell Dev Biol 6:47
Booth, K T; Kahrizi, K; Babanejad, M et al. (2018) Variants in CIB2 cause DFNB48 and not USH1J. Clin Genet 93:812-821
Booth, Kevin T; Kahrizi, Kimia; Najmabadi, Hossein et al. (2018) Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment. J Med Genet 55:555-560
Booth, Kevin T; Askew, James W; Talebizadeh, Zohreh et al. (2018) Splice-altering variant in COL11A1 as a cause of nonsyndromic hearing loss DFNA37. Genet Med :
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Milon, BĂ©atrice; Mitra, Sunayana; Song, Yang et al. (2018) The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice. Biol Sex Differ 9:12
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Yoshimura, Hidekane; Shibata, Seiji B; Ranum, Paul T et al. (2018) Enhanced viral-mediated cochlear gene delivery in adult mice by combining canal fenestration with round window membrane inoculation. Sci Rep 8:2980
Booth, Kevin T; Azaiez, Hela; Kahrizi, Kimia et al. (2018) Exonic mutations and exon skipping: Lessons learned from DFNA5. Hum Mutat 39:433-440

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