Abstract Details

Title Will You Get Stuck? Predicting Trafficking Deficient SCN1B Mutations from Localization and Amino Acid Change

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 6-012

Objective To analyze the localization and amino acid property differences between SCN1B mutations with and without trafficking deficits.

Background Voltage-gated sodium channels are heterotrimeric complexes of α and β subunits. Mutations of the β1 subunit, encoded by the SCN1B gene, are linked with numerous diseases including epilepsy and Sudden Unexpected Death in Epilepsy (SUDEP). Some of these mutations result in a trafficking deficient protein, but to date the only way to determine trafficking deficiency is to perform in vitro experiments. We hypothesize that the specific biochemical properties and localization of these mutations may be associated with trafficking deficient β subunits. Identification of the mutation properties associated with trafficking deficiencies could provide an opportunity for targeted therapeutic intervention.

Design/Methods A literature review was conducted using Pubmed to identify studies that tested whether specific SCN1B missense mutations were trafficking deficient. Data on the mutations were tabulated for analysis, including localization within the protein and biochemical properties of the amino acid change.

Results Trafficking characteristics are only known for a minority of SCN1B mutations. C121W, I106F, and R85H are known to be not trafficking deficient. They are all localized within the immunoglobulin (Ig) loop of the protein and maintain the polarity and charge of the mutated amino acid. In comparison, D25N and R125C are trafficking deficient. These mutations localize outside the Ig loop and result in a missense mutation that alters polarity of the mutated amino acid.

Conclusions Based on the limited data available, mutations known to be trafficking deficient seem to localize preferentially outside the Ig loop and result in missense mutations of altered polarity. These results will need to be confirmed through in vitro studies of other mutations. In the long term, early identification of mutations with these biochemical properties and localization may result in opportunities for therapeutic intervention tailored to trafficking-deficient mutations.

Authors/Disclosures
Rachel J. Saban, MD (University of Colorado School of Medicine) PRESENTER	Dr. Saban has nothing to disclose.
	No disclosure on file
Meaghan Berns, MD	Dr. Berns has nothing to disclose.
Gustavo A. Patino, MD, PhD (Western Michigan University Homer Stryker MD School of Medicine)	Dr. Patino has nothing to disclose.

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