Gill, J.L., Tsai, K.L., Krey, C., Noorai, R.E., Vanbellinghen, J-F., Garosi, L., Shelton, G.D., Clark, L.A. and Harvey, R.J. (2012) A canine BCAN microdeletion associated with episodic falling syndrome. Neurobiology of Disease, 45 (1). pp. 130-136. 10.1016/j.nbd.2011.07.014.
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Episodic falling syndrome (EFS) is a canine paroxysmal hypertonicity disorder found in Cavalier King Charles spaniels. Episodes are triggered by exercise, stress or excitement and characterized by progressive hypertonicity throughout the thoracic and pelvic limbs, resulting in a characteristic 'deer-stalking' position and/or collapse. We used a genome-wide association strategy to map the EFS locus to a 3.48Mb critical interval on canine chromosome 7. By prioritizing candidate genes on the basis of biological plausibility, we found that a 15.7kb deletion in BCAN, encoding the brain-specific extracellular matrix proteoglycan brevican, is associated with EFS. This represents a compelling causal mutation for EFS, since brevican has an essential role in the formation of perineuronal nets governing synapse stability and nerve conduction velocity. Mapping of the deletion breakpoint enabled the development of Multiplex PCR and Multiplex Ligation-dependent Probe Amplification (MLPA) genotyping tests that can accurately distinguish normal, carrier and affected animals. Wider testing of a larger population of CKCS dogs without a history of EFS from the USA revealed that carriers are extremely common (12.9%). The development of molecular genetic tests for the EFS microdeletion will allow the implementation of directed breeding programs aimed at minimizing the number of animals with EFS and enable confirmatory diagnosis and pharmacotherapy of affected dogs.
|Uncontrolled Keywords:||BCAN; Brevican; Cavalier King Charles spaniels; Episodic falling syndrome; Microdeletion|
|Departments, units and centres:||Department of Pharmacology > Department of Pharmacology|
|Journal or Publication Title:||Neurobiology of Disease|
|Deposited By:||Library Staff|
|Deposited On:||06 Oct 2011 10:13|
|Last Modified:||04 May 2012 15:06|
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