Journal article
Rare sudden unexpected death in epilepsy SCN5A variants cause changes in channel function implicating cardiac arrhythmia as a cause of death
MS Soh, RD Bagnall, C Semsarian, IE Scheffer, SF Berkovic, CA Reid
Epilepsia | Published : 2022
DOI: 10.1111/epi.17254
Abstract
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature death in epilepsy. The underlying pathological mechanisms are likely to be multifactorial. Cardiac arrhythmia has been suggested as a cause of death in some patients with SUDEP. SCN5A encodes the cardiac Nav1.5 sodium channel. SCN5A variants that result in either loss or gain of channel function cause cardiac arrhythmias. Rare SCN5A variants have been reported in SUDEP cases, but the impact of these variants on channel function is unknown. Here, we use whole-cell voltage clamp recordings to perform functional analyses of rare SCN5A SUDEP variants, p.V223G, p.I397V, and p.R523C. Expression and biophysical properties, ..
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Grants
Awarded by CURE Childhood Cancer
Funding Acknowledgements
We would like to thank Lucas Teasdale and Cherry Mao for their help with the patch-clamp rig. This work was supported by an anonymous philanthropic gift for SUDEP research (to S.F.B. and I.E.S.). C.A.R. would like to acknowledge the CURE foundation for support. C.S. and I.E.S. are recipients of National Health and Medical Research Council Practitioner Fellowships (#1154992 to C.S. and #1104831 to I.E.S.) and a Senior Investigator Fellowship (#1172897 to I.E.S.). This work was also made possible through the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme.