SCN1A Mutation Affects Circadian Rhythms in Dravet Patients, Researchers Find

A team of researchers at the University of Washington believe that they have found the reason that people with Dravet syndrome experience sleep disorders. They have found that mice with a heterozygous loss-of-function mutation in the SCN1A gene -- which encodes a sodium ion channel, NaV1.1, found in the brain -- have longer circadian periods than healthy mice. The mice also lack the ability to respond to light-induced phase shifts. Essentially, the mutation shorts out the brain's natural circadian "pacemaker."

Heterozygous loss of NaV1.1 channels is the underlying cause for Severe Myoclonic Epilepsy of Infancy (SMEI), or Dravet syndrome, which is at the most severe end of the Dravet Spectrum Disorders.

The researchers report that the use of the anticonvulsant drug tiagabine to enhance the transmission of γ-aminobutyric acid (GABA) -- the nervous system's main inhibitory neurotransmitter -- plus the antiepileptic drug clonazepam helps counteract the mutation's effects on the body's natural circadian rhythms. (Sung Han, et al., "NaV1.1 channels are critical for intercellular communication in the suprachiasmatic nucleus and for normal circadian rhythms," Proceedings of the National Academy of Sciences, published online January 5, 2012)

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