Although several neurotological disorders have been known for decades to occur in families, there have been relatively few studies of the genetics of these disorders. Recent advances in our understanding of episodic ataxia type 2 and familial hemiplegic migraine provide a model for understanding the genetic mechanisms of the more common episodic vertigo and ataxia syndromes, particularly those associated with migraine. The overall goal of this Project is to identify a genetic cause of familial benign recurrent vertigo. While this disorder is moderately common and may have non-allelic heterogeneity, we hypothesize that a subset of families will have autosomal dominant mutations in single genes that causes benign recurrent vertigo. Due to our ongoing efforts to characterize vertigo syndromes and treat patients in an active neurotology clinic, there is a large pool of patients from which to identify clear BRV families with sufficient members to be useful for genetic linkage analysis. Further, the wealth of different families will allow us to deal with significant levels of genetic heterogeneity and ultimately to fine map the disease locus or loci.
Specific Aim 1 : to document new families with familial benign recurrent vertigo. An additional set of 20 families with at least 10 individuals and 4 affecteds will be characterized each year.
Specific Aim 2 : to search for linkage with benign recurrent vertigo using a 10cM genome scan.
Specific Aim 3 : to narrow the region of linkage and identify candidate gene(s) in the linked regions identified. The identification of linkage and of candidate mutations in causative genes will yield important insights into normal and diseased vestibular function.
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