Megan Ealy - Otosclerosis

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Otosclerosis is a common form of conductive hearing loss, with a prevalence of 0.2 to 1% in white adults.  It is characterized by endochondral sclerosis of the inner ear bony labyrinth which invades the stapedio-vestibular joint, and interferes with the free motion of the stapes.  To date, several loci have been mapped in families segregating as autosomal dominant inheritance, but no gene has been found.  Additionally, several candidate-gene association studies have identified genes associated with otosclerosis.  These genes include COL1A1,  TGFB1,  BMP2,  BMP4, ACE and AGT.

My work current work involves microarray analysis to determine differentially expressed genes in otosclerotic stapes footplate samples.  Transcription factors that are found to regulate these genes are now being analyzed for genetic variants that may lead to this differential gene expression in otosclerosis.  A whole genome association study is also being conducted to look for single nucleotide polymorphisms associated with otosclerosis. So far, two candidate regions have been identified in Belgian-Dutch and French populations.  One associated region contains multiple candidate genes that are currently being studied for possible function in otosclerosis.  The other region contains RELN, which is known for its role in neuronal migration.  We are currently trying to identify a role for this gene in otosclerosis.