Journal article

Loss-of-function variants in K(v)11.1 cardiac channels as a biomarker for SUDEP

Ming S Soh, Richard D Bagnall, Mark F Bennett, Lauren E Bleakley, Erlina S Mohamed Syazwan, A Marie Phillips, Mathew DF Chiam, Chaseley E McKenzie, Michael Hildebrand, Douglas Crompton, Melanie Bahlo, Christopher Semsarian, Ingrid E Scheffer, Samuel F Berkovic, Christopher A Reid



OBJECTIVE: To compare the frequency and impact on the channel function of KCNH2 variants in SUDEP patients with epilepsy controls comprising patients older than 50 years, a group with low SUDEP risk, and establish loss-of-function KCNH2 variants as predictive biomarkers of SUDEP risk. METHODS: We searched for KCNH2 variants with a minor allele frequency of 20% reduction in maximal amplitude, were observed in 8.9% (8/90) SUDEP patients compared to 3.3% (11/332) epilepsy controls suggesting about threefold enrichment (nominal p = 0.04). KCNH2 variants that did not change channel function occurred at a similar frequency in SUDEP (2.2%; 2/90) and epilepsy control (2.7%; 9/332) cohorts (p > 0.99)..

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Awarded by National Health and Medical Research Council (NHMRC)

Awarded by National Health and Medical Research Council

Awarded by NHMRC Senior Research Fellowship

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council (NHMRC) Program Grant (10915693) to SFB, IES, and CAR and by an anonymous philanthropic gift for SUDEP research to SFB and IES. CAR would like to acknowledge the CURE foundation for support. CS and IES are recipients of a National Health and Medical Research Council Practitioner Fellowships (#1154992 to CS and #1104831 to IES) and Senior Investigator Fellowship to IES (#1172897). MB was supported by an NHMRC Senior Research Fellowship (#1102971). LEB acknowledges the support of an Australian Government Research Training Program Scholarship. This work was also made possible through the Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council (NHMRC) independent research Institute Infrastructure Support Scheme (IRIISS).