Journal article

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy

Mikko Muona, Samuel F Berkovic, Leanne M Dibbens, Karen L Oliver, Snezana Maljevic, Marta A Bayly, Tarja Joensuu, Laura Canafoglia, Silvana Franceschetti, Roberto Michelucci, Salla Markkinen, Sarah E Heron, Michael S Hildebrand, Eva Andermann, Frederick Andermann, Antonio Gambardella, Paolo Tinuper, Laura Licchetta, Ingrid E Scheffer, Chiara Criscuolo Show all



Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel sho..

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Awarded by Academy of Finland

Awarded by Wellcome Trust

Awarded by European Commission Framework Programme 7 (FP7)

Awarded by US NIH

Awarded by National Health and Medical Research Council (NHMRC) of Australia

Awarded by NHMRC Career Development Fellowship

Awarded by NHMRC Early Career Fellowship

Awarded by IonNeurONet

Awarded by German Research Foundation (DFG)

Awarded by NHMRC

Awarded by NMHRC

Funding Acknowledgements

This study was supported by the Folkhalsan Research Foundation (A.-E.L.), Academy of Finland grant 141549 (A.-E.L.), Wellcome Trust grants 089062 and 098051 (A.P.), European Commission Framework Programme 7 (FP7) project 201413 ENGAGE (A.P.), project 242167 SynSys (A.P.), Health-2010 projects 261433 BioSHare (A.P.) and project 261123 gEUVADIS (A.P.), Academy of Finland grants 251704 and 263401 (A.P.), the Sigrid Juselius Foundation (A.P.), US NIH grant RFA-HL-12-007 (A.P.), the Emil Aaltonen Foundation (M.M.), Epilepsiatutkimussaatio (M.M.), University of Helsinki Funds (M.M.), the Doctoral Programme in Biomedicine (M.M.), National Health and Medical Research Council (NHMRC) of Australia program grant 628952 (S.F.B., L.M.D. and I.E.S.), NHMRC Career Development Fellowship 1032603 (L.M.D.), NHMRC Early Career Fellowship 1016715 (S.E.H.), the German Network for Rare Diseases of the Federal Ministry of Education and Research (BMBF), IonNeurONet 01GM1105A (S. Maljevic and H.L.), the EuroEPINOMICS program of the European Science Foundation, German Research Foundation (DFG) grant Le1030/11-1 (H.L. and S. Maljevic), NHMRC program grant 400121 (S.P.) and NMHRC fellowship 1005050 (S.P.). The Florey Institute of Neuroscience and Mental Health (S.P.) is supported by government infrastructure funds from the state of Victoria.