Correlating otopathological analysis with genetic screening for existing syndromic and non-syndromic inner ear diseases is the goal of the House Ear Institute's contribution to the NIDCD's Otopathology Research Collaboration Network. The value of these correlations lies in connecting genetic diagnosis with a better understanding of disease progression and pathological sequelae, as well as the identification of targets for future treatment and, importantly, improved genetic counseling. Because of an almost complete lack of human biopsy material associated with inner ear disease, such connections remain largely unknown, and the only source of this information is the existing post-mortem temporal bone collections. For this reason, we have developed techniques for extracting and analyzing biological material (DNA and protein) from existing archival temporal bones for which relevant clinical data is cataloged and available. Here, we propose several Specific Aims designed to identify the underlying genetic mutations/genetic variants in existing temporal bone collections housed by members of our consortium, with the purpose of establishing a genotype/otopathology phenotype correlation. This has not been done consistently for any of the known genetic disorders of the inner ear, and the successful outcome of this proposal promises to provide an enhanced resource for the clinician and researcher who wish to link the etiology of inner ear disease with its otopathological outcome.

Public Health Relevance

Molecular biological techniques have only recently been applied to study the correlation of biological structure with function in normal and diseased human temporal bones. This proposal will fill the knowledge gap by performing a comprehensive genotype-phenotype correlation in four hearing disorders;1) Hereditary, 2) Meniere's, 3) Otosclerosis, and 4) NF2.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DC011962-02
Application #
8308371
Study Section
Special Emphasis Panel (ZDC1-SRB-R (32))
Program Officer
Cyr, Janet
Project Start
2011-09-01
Project End
2016-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$487,839
Indirect Cost
$249,035
Name
House Research Institute
Department
Type
DUNS #
062076989
City
Los Angeles
State
CA
Country
United States
Zip Code
90057
Linthicum Jr, Fred H; Doherty, Joni; Webster, Paul et al. (2014) The periductal channels of the endolymphatic duct, hydrodynamic implications. Otolaryngol Head Neck Surg 150:441-7
Doherty, Joni; Go, John L; Linthicum Jr, Fred H (2014) Neurofibromatosis 2 invasion of the internal auditory canal wall: clinical significance. Otol Neurotol 35:1662-8
Doherty, Joni K; Linthicum Jr, Fred H (2013) Adipose replacing intracochlear architecture after meningioma removal. Otol Neurotol 34:e8-9
Hoa, Michael; Linthicum Jr, Fred H (2013) Spiral ganglion deficiency in adult-onset deafness-dystonia syndrome. Otol Neurotol 34:e130-1
Cassis, Adam; Doherty, Joni K; Daspit, C Phillip et al. (2013) Short-term histopathology effects of gamma knife radiosurgery on a vestibular schwannoma. Otolaryngol Head Neck Surg 148:1056-8
Hoa, M; House, J W; Linthicum, F H et al. (2013) Petrous apex cholesterol granuloma: pictorial review of radiological considerations in diagnosis and surgical histopathology. J Laryngol Otol 127:339-48
Kimmel, Rachel A; Doherty, Joni; Slattery 3rd, William H et al. (2013) Recurrent schwannoma postirradiation: histological review reveals mixed schwannoma and meningioma. Otolaryngol Head Neck Surg 148:886-8