De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy.

2.50
Hdl Handle:
http://hdl.handle.net/11287/620720
Title:
De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy.
Authors:
Ambrosino, P.; Soldovieri, M. V.; Bast, T.; Turnpenny, Peter D.; Uhrig, S.; Biskup, S.; Döcker, M.; Fleck, T.; Mosca, I.; Manocchio, L.; Iraci, N.; Taglialatela, M.; Lemke, J. R.
Abstract:
Variants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report two females with de novo variants in KCNT2 with West syndrome followed by Lennox-Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine-responsive gain-of-function effects, we treated one of the girls with quinidine add-on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2-related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1-related disorders but also represents a further example for possible precision medicine approaches. This article is protected by copyright. All rights reserved.
Citation:
De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy. 2018 Ann. Neurol.
Publisher:
Wiley
Journal:
Annals of neurology
Issue Date:
8-May-2018
URI:
http://hdl.handle.net/11287/620720
DOI:
10.1002/ana.25248
PubMed ID:
29740868
Additional Links:
https://doi.org/10.1002/ana.25248
Type:
Journal Article
Language:
en
ISSN:
1531-8249
Appears in Collections:
Clinical Genetics (Peninsula Genetics); 2018 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorAmbrosino, P.en
dc.contributor.authorSoldovieri, M. V.en
dc.contributor.authorBast, T.en
dc.contributor.authorTurnpenny, Peter D.en
dc.contributor.authorUhrig, S.en
dc.contributor.authorBiskup, S.en
dc.contributor.authorDöcker, M.en
dc.contributor.authorFleck, T.en
dc.contributor.authorMosca, I.en
dc.contributor.authorManocchio, L.en
dc.contributor.authorIraci, N.en
dc.contributor.authorTaglialatela, M.en
dc.contributor.authorLemke, J. R.en
dc.date.accessioned2018-06-22T15:20:04Z-
dc.date.available2018-06-22T15:20:04Z-
dc.date.issued2018-05-08-
dc.identifier.citationDe novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy. 2018 Ann. Neurol.en
dc.identifier.issn1531-8249-
dc.identifier.pmid29740868-
dc.identifier.doi10.1002/ana.25248-
dc.identifier.urihttp://hdl.handle.net/11287/620720-
dc.description.abstractVariants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report two females with de novo variants in KCNT2 with West syndrome followed by Lennox-Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine-responsive gain-of-function effects, we treated one of the girls with quinidine add-on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2-related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1-related disorders but also represents a further example for possible precision medicine approaches. This article is protected by copyright. All rights reserved.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttps://doi.org/10.1002/ana.25248en
dc.rightsArchived with thanks to Annals of neurologyen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.titleDe novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy.en
dc.typeJournal Articleen
dc.identifier.journalAnnals of neurologyen
dc.type.versionIn press (epub ahead of print)en

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