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Mutations in KCNT 1 cause a spectrum of focal epilepsies
Author(s) -
Møller Rikke S.,
Heron Sarah E.,
Larsen Line H. G.,
Lim Chiao Xin,
Ricos Michael G.,
Bayly Marta A.,
Kempen Marjan J. A.,
Klinkenberg Sylvia,
Andrews Ian,
Kelley Kent,
Ronen Gabriel M.,
Callen David,
McMahon Jacinta M.,
Yendle Simone C.,
Carvill Gemma L.,
Mefford Heather C.,
Nabbout Rima,
Poduri Annapurna,
Striano Pasquale,
Baglietto Maria G.,
Zara Federico,
Smith Nicholas J.,
Pridmore Clair,
Gardella Elena,
Nikanorova Marina,
Dahl Hans Atli,
Gellert Pia,
Scheffer Ingrid E.,
Gunning Boudewijn,
KraghOlsen Bente,
Dibbens Leanne M.
Publication year - 2015
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13071
Subject(s) - epilepsy , penetrance , mutation , phenotype , biology , genetics , epilepsy syndromes , medicine , neuroscience , bioinformatics , gene
Summary Autosomal dominant mutations in the sodium‐gated potassium channel subunit gene KCNT 1 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 KCNT 1 , we examined individuals affected with focal epilepsy or an epileptic encephalopathy for mutations in the gene. We identified KCNT 1 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 KCNT 1 mutations, we observed incomplete penetrance. It is notable that we report that the one KCNT 1 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 KCNT 1 mutations are not straightforward. We demonstrate that KCNT 1 mutations are highly pleiotropic and are associated with phenotypes other than ADNFLE and MMFSI . KCNT 1 mutations are now associated with Ohtahara syndrome, MMFSI , and nocturnal focal epilepsy. They may also be associated with multifocal epilepsy and cardiac disturbances.