Mutations in KCNT1 cause a spectrum of focal epilepsies

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dc.contributor.authorMøller, R.
dc.contributor.authorHeron, S.
dc.contributor.authorLarsen, L.
dc.contributor.authorLim, C.
dc.contributor.authorRicos, M.
dc.contributor.authorBayly, M.
dc.contributor.authorVan Kempen, M.
dc.contributor.authorKlinkenberg, S.
dc.contributor.authorAndrews, I.
dc.contributor.authorKelley, K.
dc.contributor.authorRonen, G.
dc.contributor.authorCallen, D.
dc.contributor.authorMcMahon, J.
dc.contributor.authorYendle, S.
dc.contributor.authorCarvill, G.
dc.contributor.authorMefford, H.
dc.contributor.authorNabbout, R.
dc.contributor.authorPoduri, A.
dc.contributor.authorStriano, P.
dc.contributor.authorBaglietto, M.
dc.contributor.authoret al.
dc.date.issued2015
dc.description.abstractAutosomal dominant mutations in the sodium-gated potassium channel subunit gene KCNT1 have been associated with two distinct seizure syndromes, nocturnal frontal lobe epilepsy (NFLE) and malignant migrating focal seizures of infancy (MMFSI). To further explore the phenotypic spectrum associated with KCNT1, we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT1 mutations in 12 previously unreported patients with focal epilepsy, multifocal epilepsy, cardiac arrhythmia, and in a family with sudden unexpected death in epilepsy (SUDEP), in addition to patients with NFLE and MMFSI. In contrast to the 100% penetrance so far reported for KCNT1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT1 mutation, p.Arg398Gln, can lead to either of the two distinct phenotypes, ADNFLE or MMFSI, even within the same family. This indicates that genotype-phenotype relationships for KCNT1 mutations are not straightforward. We demonstrate that KCNT1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI. KCNT1 mutations are now associated with Ohtahara syndrome, MMFSI, and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances.
dc.description.statementofresponsibilityRikke S. Møller, Sarah E. Heron ... Nicholas J. Smith ... Leanne M. Dibbens
dc.identifier.citationEpilepsia, 2015; 56(9):e114-e120
dc.identifier.doi10.1111/epi.13071
dc.identifier.issn0013-9580
dc.identifier.issn1528-1167
dc.identifier.orcidHeron, S. [0000-0001-8759-6748]
dc.identifier.orcidSmith, N. [0000-0003-2409-9239]
dc.identifier.urihttp://hdl.handle.net/2440/99797
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016715
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1032603
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/628952
dc.rights© 2015 International League Against Epilepsy
dc.source.urihttps://doi.org/10.1111/epi.13071
dc.subjectKCNT1; Autosomal dominant nocturnal frontal lobe epilepsy; Epileptic encephalopathy; Cardiac arrhythmia; Sudden unexpected death in epilepsy
dc.titleMutations in KCNT1 cause a spectrum of focal epilepsies
dc.typeJournal article
pubs.publication-statusPublished

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