KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine

CJ Milligan; M Li; EV Gazina; SE Heron; U Nair; C Trager; CA Reid; A Venkat; DP Younkin; DJ Dlugos; S Petrovski; DB Goldstein; LM Dibbens; IE Scheffer; SF Berkovic; S Petrou

Journal article

KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine

CJ Milligan, M Li, EV Gazina, SE Heron, U Nair, C Trager, CA Reid, A Venkat, DP Younkin, DJ Dlugos, S Petrovski, DB Goldstein, LM Dibbens, IE Scheffer, SF Berkovic, S Petrou

Annals of Neurology | Published : 2014

DOI: 10.1002/ana.24128

Abstract

Objective Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating focal seizures (EIMFS). More recently, a whole exome sequencing study of epileptic encephalopathies identified an additional de novo mutation in 1 proband with EIMFS. We aim to investigate the electrophysiological and pharmacological characteristics of hKCNT1 mutations and examine developmental expression levels. Methods Here we use a Xenopus laevis oocyte-based automated 2-electrode voltage clamp assay. The effects of quinidine (100 and 300μM) are also tested. Using quantitative reverse transcriptase polymerase chain reaction, the relative l..

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University of Melbourne Researchers

Melody Li Author

Christopher Reid Author

Slave Petrovski Author

Ingrid Scheffer Author

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Grants

Awarded by National Institute of Neurological Disorders and Stroke

Funding Acknowledgements

This work was supported by the Victorian Government through the Operational Infrastructure Scheme. This work was supported by the following grants from the National Health and Medical Research Council of Australia: Program Grant 628952 to S. F. B., I. E. S., S. Petrou, and L. M. D.; Training Fellowship 1016715 to S. E. H.; Senior Research Fellowship 1005050 to S. Petrou; Australia Fellowship 466671 to S. F. B.; Practitioner Fellowship 1006110 to I. E. S.; and Career Development Fellowship 1032603 to L. M. D. We thank the families for their participation in this study; Dr D. Lowenstein and colleagues from the Epilepsy Phenome/Genome Project (epgp.org; supported by grant NS053998 from the NIH National Institute of Neurological Disorders and Stroke [NINDS]) and Epi4K (epi4K.org; supported by grants NS053998, NS077274, NS077303, and NS077276 from NINDS) for their collaborative efforts that led to the identification of the individual with the P924L mutation included in this study.