Among white adults, otosclerosis is the single most common cause of hearing impairment. The disease is caused by abnormal bone homeostasis of the otic capsule, which usually results in a conductive hearing loss due to fixation of the stapes footplate, although sensorineural hearing loss also may occur. The etiology of otosclerosis is unknown, and both genetic and environmental factors have been implicated. Although the genetics of otosclerosis are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. Using two large families showing this type of Mendelian inheritance pattern, we have localized two otosclerosis-causing genes, OTSCI and OTSC2. We also have shown that at least one additional locus, OTSC3, exists. Continuing on this initial body of work, we propose to: 1) Clone the OTSCI and OTSC2 genes; 2) Identify novel otosclerosis loci by linkage analysis; 3) Identify novel otosclerosis loci by linkage and linkage disequilibrium analyses in families from Greece; 4) Identify novel otosclerosis loci by non-parametric linkage analysis using affected sib pairs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005218-02
Application #
6620382
Study Section
Special Emphasis Panel (ZRG1-IFCN-6 (01))
Program Officer
Watson, Bracie
Project Start
2002-05-01
Project End
2007-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
2
Fiscal Year
2003
Total Cost
$303,144
Indirect Cost
Name
University of Iowa
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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Ali, Insaf Bel Hadj; Thys, Melissa; Beltaief, Najeh et al. (2007) Clinical and genetic analysis of two Tunisian otosclerosis families. Am J Med Genet A 143A:1653-60
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Thys, Melissa; Van Den Bogaert, Kris; Iliadou, Vassiliki et al. (2007) A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1. Eur J Hum Genet 15:362-8
Chen, W; Meyer, N C; McKenna, M J et al. (2007) Single-nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis. Clin Genet 71:406-14

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