Mutations in KCNT1 cause a spectrum of focal epilepsies.
Identifieur interne : 002960 ( PubMed/Corpus ); précédent : 002959; suivant : 002961Mutations in KCNT1 cause a spectrum of focal epilepsies.
Auteurs : Rikke S. M Ller ; Sarah E. Heron ; Line H G. Larsen ; Chiao Xin Lim ; Michael G. Ricos ; Marta A. Bayly ; Marjan J A. Van Kempen ; Sylvia Klinkenberg ; Ian Andrews ; Kent Kelley ; Gabriel M. Ronen ; David Callen ; Jacinta M. Mcmahon ; Simone C. Yendle ; Gemma L. Carvill ; Heather C. Mefford ; Rima Nabbout ; Annapurna Poduri ; Pasquale Striano ; Maria G. Baglietto ; Federico Zara ; Nicholas J. Smith ; Clair Pridmore ; Elena Gardella ; Marina Nikanorova ; Hans Atli Dahl ; Pia Gellert ; Ingrid E. Scheffer ; Boudewijn Gunning ; Bente Kragh-Olsen ; Leanne M. DibbensSource :
- Epilepsia [ 1528-1167 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Nerve Tissue Proteins, Potassium Channels.
- genetics : Epilepsies, Partial, Mutation, Sudden Infant Death.
- Adolescent, Age of Onset, Child, Child, Preschool, Female, Humans, Infant, Male.
Abstract
Autosomal 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.
DOI: 10.1111/epi.13071
PubMed: 26122718
Links to Exploration step
pubmed:26122718Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Mutations in KCNT1 cause a spectrum of focal epilepsies.</title><author><name sortKey="M Ller, Rikke S" sort="M Ller, Rikke S" uniqKey="M Ller R" first="Rikke S" last="M Ller">Rikke S. M Ller</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Heron, Sarah E" sort="Heron, Sarah E" uniqKey="Heron S" first="Sarah E" last="Heron">Sarah E. Heron</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Larsen, Line H G" sort="Larsen, Line H G" uniqKey="Larsen L" first="Line H G" last="Larsen">Line H G. Larsen</name><affiliation><nlm:affiliation>Amplexa Genetics, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Lim, Chiao Xin" sort="Lim, Chiao Xin" uniqKey="Lim C" first="Chiao Xin" last="Lim">Chiao Xin Lim</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ricos, Michael G" sort="Ricos, Michael G" uniqKey="Ricos M" first="Michael G" last="Ricos">Michael G. Ricos</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Bayly, Marta A" sort="Bayly, Marta A" uniqKey="Bayly M" first="Marta A" last="Bayly">Marta A. Bayly</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Van Kempen, Marjan J A" sort="Van Kempen, Marjan J A" uniqKey="Van Kempen M" first="Marjan J A" last="Van Kempen">Marjan J A. Van Kempen</name><affiliation><nlm:affiliation>Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Klinkenberg, Sylvia" sort="Klinkenberg, Sylvia" uniqKey="Klinkenberg S" first="Sylvia" last="Klinkenberg">Sylvia Klinkenberg</name><affiliation><nlm:affiliation>Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Andrews, Ian" sort="Andrews, Ian" uniqKey="Andrews I" first="Ian" last="Andrews">Ian Andrews</name><affiliation><nlm:affiliation>Neurology Service, Sydney Children's Hospital, Randwick, New South Wales, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kelley, Kent" sort="Kelley, Kent" uniqKey="Kelley K" first="Kent" last="Kelley">Kent Kelley</name><affiliation><nlm:affiliation>NorthShore University HealthSystem, Evanston, Illinois, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Ronen, Gabriel M" sort="Ronen, Gabriel M" uniqKey="Ronen G" first="Gabriel M" last="Ronen">Gabriel M. Ronen</name><affiliation><nlm:affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Callen, David" sort="Callen, David" uniqKey="Callen D" first="David" last="Callen">David Callen</name><affiliation><nlm:affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmahon, Jacinta M" sort="Mcmahon, Jacinta M" uniqKey="Mcmahon J" first="Jacinta M" last="Mcmahon">Jacinta M. Mcmahon</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Yendle, Simone C" sort="Yendle, Simone C" uniqKey="Yendle S" first="Simone C" last="Yendle">Simone C. Yendle</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Carvill, Gemma L" sort="Carvill, Gemma L" uniqKey="Carvill G" first="Gemma L" last="Carvill">Gemma L. Carvill</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Mefford, Heather C" sort="Mefford, Heather C" uniqKey="Mefford H" first="Heather C" last="Mefford">Heather C. Mefford</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Nabbout, Rima" sort="Nabbout, Rima" uniqKey="Nabbout R" first="Rima" last="Nabbout">Rima Nabbout</name><affiliation><nlm:affiliation>Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Hospital Necker-Enfants Malades, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poduri, Annapurna" sort="Poduri, Annapurna" uniqKey="Poduri A" first="Annapurna" last="Poduri">Annapurna Poduri</name><affiliation><nlm:affiliation>Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Striano, Pasquale" sort="Striano, Pasquale" uniqKey="Striano P" first="Pasquale" last="Striano">Pasquale Striano</name><affiliation><nlm:affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Baglietto, Maria G" sort="Baglietto, Maria G" uniqKey="Baglietto M" first="Maria G" last="Baglietto">Maria G. Baglietto</name><affiliation><nlm:affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Zara, Federico" sort="Zara, Federico" uniqKey="Zara F" first="Federico" last="Zara">Federico Zara</name><affiliation><nlm:affiliation>Laboratory of Neurogenetics, Department of Neurosciences, G. Gaslini Institute, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Smith, Nicholas J" sort="Smith, Nicholas J" uniqKey="Smith N" first="Nicholas J" last="Smith">Nicholas J. Smith</name><affiliation><nlm:affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Pridmore, Clair" sort="Pridmore, Clair" uniqKey="Pridmore C" first="Clair" last="Pridmore">Clair Pridmore</name><affiliation><nlm:affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gardella, Elena" sort="Gardella, Elena" uniqKey="Gardella E" first="Elena" last="Gardella">Elena Gardella</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Nikanorova, Marina" sort="Nikanorova, Marina" uniqKey="Nikanorova M" first="Marina" last="Nikanorova">Marina Nikanorova</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dahl, Hans Atli" sort="Dahl, Hans Atli" uniqKey="Dahl H" first="Hans Atli" last="Dahl">Hans Atli Dahl</name><affiliation><nlm:affiliation>Amplexa Genetics, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Gellert, Pia" sort="Gellert, Pia" uniqKey="Gellert P" first="Pia" last="Gellert">Pia Gellert</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Scheffer, Ingrid E" sort="Scheffer, Ingrid E" uniqKey="Scheffer I" first="Ingrid E" last="Scheffer">Ingrid E. Scheffer</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gunning, Boudewijn" sort="Gunning, Boudewijn" uniqKey="Gunning B" first="Boudewijn" last="Gunning">Boudewijn Gunning</name><affiliation><nlm:affiliation>SEIN - Epilepsy Institutes in the Netherlands Foundation, Zwolle, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Kragh Olsen, Bente" sort="Kragh Olsen, Bente" uniqKey="Kragh Olsen B" first="Bente" last="Kragh-Olsen">Bente Kragh-Olsen</name><affiliation><nlm:affiliation>Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dibbens, Leanne M" sort="Dibbens, Leanne M" uniqKey="Dibbens L" first="Leanne M" last="Dibbens">Leanne M. Dibbens</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26122718</idno><idno type="pmid">26122718</idno><idno type="doi">10.1111/epi.13071</idno><idno type="wicri:Area/PubMed/Corpus">002960</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002960</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Mutations in KCNT1 cause a spectrum of focal epilepsies.</title><author><name sortKey="M Ller, Rikke S" sort="M Ller, Rikke S" uniqKey="M Ller R" first="Rikke S" last="M Ller">Rikke S. M Ller</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Heron, Sarah E" sort="Heron, Sarah E" uniqKey="Heron S" first="Sarah E" last="Heron">Sarah E. Heron</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Larsen, Line H G" sort="Larsen, Line H G" uniqKey="Larsen L" first="Line H G" last="Larsen">Line H G. Larsen</name><affiliation><nlm:affiliation>Amplexa Genetics, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Lim, Chiao Xin" sort="Lim, Chiao Xin" uniqKey="Lim C" first="Chiao Xin" last="Lim">Chiao Xin Lim</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Ricos, Michael G" sort="Ricos, Michael G" uniqKey="Ricos M" first="Michael G" last="Ricos">Michael G. Ricos</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Bayly, Marta A" sort="Bayly, Marta A" uniqKey="Bayly M" first="Marta A" last="Bayly">Marta A. Bayly</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Van Kempen, Marjan J A" sort="Van Kempen, Marjan J A" uniqKey="Van Kempen M" first="Marjan J A" last="Van Kempen">Marjan J A. Van Kempen</name><affiliation><nlm:affiliation>Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Klinkenberg, Sylvia" sort="Klinkenberg, Sylvia" uniqKey="Klinkenberg S" first="Sylvia" last="Klinkenberg">Sylvia Klinkenberg</name><affiliation><nlm:affiliation>Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Andrews, Ian" sort="Andrews, Ian" uniqKey="Andrews I" first="Ian" last="Andrews">Ian Andrews</name><affiliation><nlm:affiliation>Neurology Service, Sydney Children's Hospital, Randwick, New South Wales, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Kelley, Kent" sort="Kelley, Kent" uniqKey="Kelley K" first="Kent" last="Kelley">Kent Kelley</name><affiliation><nlm:affiliation>NorthShore University HealthSystem, Evanston, Illinois, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Ronen, Gabriel M" sort="Ronen, Gabriel M" uniqKey="Ronen G" first="Gabriel M" last="Ronen">Gabriel M. Ronen</name><affiliation><nlm:affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Callen, David" sort="Callen, David" uniqKey="Callen D" first="David" last="Callen">David Callen</name><affiliation><nlm:affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Mcmahon, Jacinta M" sort="Mcmahon, Jacinta M" uniqKey="Mcmahon J" first="Jacinta M" last="Mcmahon">Jacinta M. Mcmahon</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Yendle, Simone C" sort="Yendle, Simone C" uniqKey="Yendle S" first="Simone C" last="Yendle">Simone C. Yendle</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Carvill, Gemma L" sort="Carvill, Gemma L" uniqKey="Carvill G" first="Gemma L" last="Carvill">Gemma L. Carvill</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Mefford, Heather C" sort="Mefford, Heather C" uniqKey="Mefford H" first="Heather C" last="Mefford">Heather C. Mefford</name><affiliation><nlm:affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Nabbout, Rima" sort="Nabbout, Rima" uniqKey="Nabbout R" first="Rima" last="Nabbout">Rima Nabbout</name><affiliation><nlm:affiliation>Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Hospital Necker-Enfants Malades, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poduri, Annapurna" sort="Poduri, Annapurna" uniqKey="Poduri A" first="Annapurna" last="Poduri">Annapurna Poduri</name><affiliation><nlm:affiliation>Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.</nlm:affiliation></affiliation></author><author><name sortKey="Striano, Pasquale" sort="Striano, Pasquale" uniqKey="Striano P" first="Pasquale" last="Striano">Pasquale Striano</name><affiliation><nlm:affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Baglietto, Maria G" sort="Baglietto, Maria G" uniqKey="Baglietto M" first="Maria G" last="Baglietto">Maria G. Baglietto</name><affiliation><nlm:affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Zara, Federico" sort="Zara, Federico" uniqKey="Zara F" first="Federico" last="Zara">Federico Zara</name><affiliation><nlm:affiliation>Laboratory of Neurogenetics, Department of Neurosciences, G. Gaslini Institute, Genova, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Smith, Nicholas J" sort="Smith, Nicholas J" uniqKey="Smith N" first="Nicholas J" last="Smith">Nicholas J. Smith</name><affiliation><nlm:affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Pridmore, Clair" sort="Pridmore, Clair" uniqKey="Pridmore C" first="Clair" last="Pridmore">Clair Pridmore</name><affiliation><nlm:affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gardella, Elena" sort="Gardella, Elena" uniqKey="Gardella E" first="Elena" last="Gardella">Elena Gardella</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Nikanorova, Marina" sort="Nikanorova, Marina" uniqKey="Nikanorova M" first="Marina" last="Nikanorova">Marina Nikanorova</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dahl, Hans Atli" sort="Dahl, Hans Atli" uniqKey="Dahl H" first="Hans Atli" last="Dahl">Hans Atli Dahl</name><affiliation><nlm:affiliation>Amplexa Genetics, Odense, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Gellert, Pia" sort="Gellert, Pia" uniqKey="Gellert P" first="Pia" last="Gellert">Pia Gellert</name><affiliation><nlm:affiliation>Danish Epilepsy Center, Dianalund, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Scheffer, Ingrid E" sort="Scheffer, Ingrid E" uniqKey="Scheffer I" first="Ingrid E" last="Scheffer">Ingrid E. Scheffer</name><affiliation><nlm:affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Gunning, Boudewijn" sort="Gunning, Boudewijn" uniqKey="Gunning B" first="Boudewijn" last="Gunning">Boudewijn Gunning</name><affiliation><nlm:affiliation>SEIN - Epilepsy Institutes in the Netherlands Foundation, Zwolle, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Kragh Olsen, Bente" sort="Kragh Olsen, Bente" uniqKey="Kragh Olsen B" first="Bente" last="Kragh-Olsen">Bente Kragh-Olsen</name><affiliation><nlm:affiliation>Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.</nlm:affiliation></affiliation></author><author><name sortKey="Dibbens, Leanne M" sort="Dibbens, Leanne M" uniqKey="Dibbens L" first="Leanne M" last="Dibbens">Leanne M. Dibbens</name><affiliation><nlm:affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Epilepsia</title><idno type="eISSN">1528-1167</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Age of Onset</term><term>Child</term><term>Child, Preschool</term><term>Epilepsies, Partial (genetics)</term><term>Female</term><term>Humans</term><term>Infant</term><term>Male</term><term>Mutation (genetics)</term><term>Nerve Tissue Proteins (genetics)</term><term>Potassium Channels (genetics)</term><term>Sudden Infant Death (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Nerve Tissue Proteins</term><term>Potassium Channels</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Epilepsies, Partial</term><term>Mutation</term><term>Sudden Infant Death</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adolescent</term><term>Age of Onset</term><term>Child</term><term>Child, Preschool</term><term>Female</term><term>Humans</term><term>Infant</term><term>Male</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Autosomal 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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26122718</PMID><DateCreated><Year>2015</Year><Month>09</Month><Day>05</Day></DateCreated><DateCompleted><Year>2016</Year><Month>04</Month><Day>29</Day></DateCompleted><DateRevised><Year>2015</Year><Month>09</Month><Day>05</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1528-1167</ISSN><JournalIssue CitedMedium="Internet"><Volume>56</Volume><Issue>9</Issue><PubDate><Year>2015</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Epilepsia</Title><ISOAbbreviation>Epilepsia</ISOAbbreviation></Journal><ArticleTitle>Mutations in KCNT1 cause a spectrum of focal epilepsies.</ArticleTitle><Pagination><MedlinePgn>e114-20</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1111/epi.13071</ELocationID><Abstract><AbstractText>Autosomal 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.</AbstractText><CopyrightInformation>Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Møller</LastName><ForeName>Rikke S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Danish Epilepsy Center, Dianalund, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heron</LastName><ForeName>Sarah E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Larsen</LastName><ForeName>Line H G</ForeName><Initials>LH</Initials><AffiliationInfo><Affiliation>Amplexa Genetics, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lim</LastName><ForeName>Chiao Xin</ForeName><Initials>CX</Initials><AffiliationInfo><Affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ricos</LastName><ForeName>Michael G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bayly</LastName><ForeName>Marta A</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Kempen</LastName><ForeName>Marjan J A</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Klinkenberg</LastName><ForeName>Sylvia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Neurology, Maastricht University Medical Center, Maastricht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Andrews</LastName><ForeName>Ian</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Neurology Service, Sydney Children's Hospital, Randwick, New South Wales, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Women's and Children's Health, University of New South Wales, Kensington, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kelley</LastName><ForeName>Kent</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>NorthShore University HealthSystem, Evanston, Illinois, U.S.A.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ronen</LastName><ForeName>Gabriel M</ForeName><Initials>GM</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Callen</LastName><ForeName>David</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McMahon</LastName><ForeName>Jacinta M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yendle</LastName><ForeName>Simone C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carvill</LastName><ForeName>Gemma L</ForeName><Initials>GL</Initials><AffiliationInfo><Affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mefford</LastName><ForeName>Heather C</ForeName><Initials>HC</Initials><AffiliationInfo><Affiliation>Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, U.S.A.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nabbout</LastName><ForeName>Rima</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Pediatric Neurology, Reference Center for Rare Epilepsies, Hospital Necker-Enfants Malades, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poduri</LastName><ForeName>Annapurna</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Epilepsy Genetics Program, Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, U.S.A.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Striano</LastName><ForeName>Pasquale</ForeName><Initials>P</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-6065-1476</Identifier><AffiliationInfo><Affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baglietto</LastName><ForeName>Maria G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, G. Gaslini Institute, University of Genoa, Genova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zara</LastName><ForeName>Federico</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Laboratory of Neurogenetics, Department of Neurosciences, G. Gaslini Institute, Genova, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Smith</LastName><ForeName>Nicholas J</ForeName><Initials>NJ</Initials><AffiliationInfo><Affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pridmore</LastName><ForeName>Clair</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Neurology, Women's and Children's Health Network, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gardella</LastName><ForeName>Elena</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Danish Epilepsy Center, Dianalund, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nikanorova</LastName><ForeName>Marina</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Danish Epilepsy Center, Dianalund, Denmark.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dahl</LastName><ForeName>Hans Atli</ForeName><Initials>HA</Initials><AffiliationInfo><Affiliation>Amplexa Genetics, Odense, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gellert</LastName><ForeName>Pia</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Danish Epilepsy Center, Dianalund, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scheffer</LastName><ForeName>Ingrid E</ForeName><Initials>IE</Initials><AffiliationInfo><Affiliation>Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gunning</LastName><ForeName>Boudewijn</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>SEIN - Epilepsy Institutes in the Netherlands Foundation, Zwolle, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kragh-Olsen</LastName><ForeName>Bente</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dibbens</LastName><ForeName>Leanne M</ForeName><Initials>LM</Initials><AffiliationInfo><Affiliation>Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>06</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Epilepsia</MedlineTA><NlmUniqueID>2983306R</NlmUniqueID><ISSNLinking>0013-9580</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C585122">KCNT1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009419">Nerve Tissue Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015221">Potassium Channels</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000293" MajorTopicYN="N">Adolescent</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017668" MajorTopicYN="N">Age of Onset</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002648" MajorTopicYN="N">Child</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002675" MajorTopicYN="N">Child, Preschool</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004828" MajorTopicYN="N">Epilepsies, Partial</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D007223" MajorTopicYN="N">Infant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009154" MajorTopicYN="N">Mutation</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D009419" MajorTopicYN="N">Nerve Tissue Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D015221" MajorTopicYN="N">Potassium Channels</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D013398" MajorTopicYN="N">Sudden Infant Death</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Autosomal dominant nocturnal frontal lobe epilepsy</Keyword><Keyword MajorTopicYN="N">Cardiac arrhythmia</Keyword><Keyword MajorTopicYN="N">Epileptic encephalopathy</Keyword><Keyword MajorTopicYN="N">KCNT1</Keyword><Keyword MajorTopicYN="N">Sudden unexpected death in epilepsy</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="accepted"><Year>2015</Year><Month>06</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>7</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>7</Month><Day>1</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2016</Year><Month>4</Month><Day>30</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26122718</ArticleId><ArticleId IdType="doi">10.1111/epi.13071</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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