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.
| 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 |
| Sloan-Heggen, Christina M; Smith, Richard J H (2016) Navigating genetic diagnostics in patients with hearing loss. Curr Opin Pediatr 28:705-712 |
| Ealy, Megan; Meyer, Nicole C; Corchado, Johnny Cruz et al. (2014) Rare variants in BMP2 and BMP4 found in otosclerosis patients reduce Smad signaling. Otol Neurotol 35:395-400 |
| Ealy, Megan; Chen, Wenjie; Ryu, Gi-Yung et al. (2008) Gene expression analysis of human otosclerotic stapedial footplates. Hear Res 240:80-6 |
| Schrauwen, Isabelle; Thys, Melissa; Vanderstraeten, Kathleen et al. (2008) Association of bone morphogenetic proteins with otosclerosis. J Bone Miner Res 23:507-16 |
| Bel Hadj Ali, Insaf; Thys, Melissa; Beltaief, Najeh et al. (2008) A new locus for otosclerosis, OTSC8, maps to the pericentromeric region of chromosome 9. Hum Genet 123:267-72 |
| 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 |
| Thys, Melissa; Schrauwen, Isabelle; Vanderstraeten, Kathleen et al. (2007) The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations. Hum Mol Genet 16:2021-30 |
| 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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