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dc.contributor.authorGripp, Karen
dc.contributor.authorSmithson, SF
dc.contributor.authorScurr, IJ
dc.contributor.authorBaptista, Julia
dc.contributor.authorMajumdar, A
dc.contributor.authorPierre, G
dc.contributor.authorWilliams, M
dc.contributor.authorHenderson, LB
dc.contributor.authorWentzensen, IM
dc.contributor.authorMcLaughlin, H
dc.contributor.authorLeeuwen, Lisette
dc.contributor.authorSimon, MEH
dc.contributor.authorvan Binsbergen, E
dc.contributor.authorDinulos, MBP
dc.contributor.authorKaplan, JD
dc.contributor.authorMcRae, A
dc.contributor.authorSuperti-Furga, A
dc.contributor.authorGood, J-M
dc.contributor.authorKutsche, K
dc.date.accessioned2022-05-03T18:18:58Z
dc.date.issued2021-09
dc.identifier.issn1018-4813
dc.identifier.issn1476-5438
dc.identifier.urihttp://hdl.handle.net/10026.1/19169
dc.description.abstract

<jats:title>Abstract</jats:title><jats:p>Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K<jats:sup>+</jats:sup> channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann–Laband and Temple–Baraitser syndromes, caused by dominant variants in <jats:italic>KCNH1</jats:italic>, FHEIG syndrome due to dominant variants in <jats:italic>KCNK4</jats:italic>, and the clinical picture associated with dominant variants in <jats:italic>KCNN3</jats:italic>. Here we review the presentation of these individuals, including five newly reported with variants in <jats:italic>KCNH1</jats:italic> and three additional individuals with <jats:italic>KCNN3</jats:italic> variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant <jats:italic>KCNN3</jats:italic>, <jats:italic>KCNH1</jats:italic>, and <jats:italic>KCNK4</jats:italic> variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K<jats:sup>+</jats:sup> conductance, referred to as syndromic neurodevelopmental K<jats:sup>+</jats:sup> channelopathies due to dominant variants in <jats:italic>KCNH1</jats:italic>, <jats:italic>KCNK4</jats:italic>, or <jats:italic>KCNN3</jats:italic>.</jats:p>

dc.format.extent1384-1395
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoeng
dc.publisherSpringer Science and Business Media LLC
dc.subjectAbnormalities, Multiple
dc.subjectAdolescent
dc.subjectAdult
dc.subjectChannelopathies
dc.subjectChild
dc.subjectCraniofacial Abnormalities
dc.subjectEther-A-Go-Go Potassium Channels
dc.subjectFemale
dc.subjectFibromatosis, Gingival
dc.subjectGain of Function Mutation
dc.subjectHallux
dc.subjectHand Deformities, Congenital
dc.subjectHumans
dc.subjectIntellectual Disability
dc.subjectMale
dc.subjectNails, Malformed
dc.subjectPhenotype
dc.subjectPotassium Channels
dc.subjectSmall-Conductance Calcium-Activated Potassium Channels
dc.subjectThumb
dc.titleSyndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies
dc.typejournal-article
dc.typeCase Reports
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000618711300001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue9
plymouth.volume29
plymouth.publication-statusPublished
plymouth.journalEuropean Journal of Human Genetics
dc.identifier.doi10.1038/s41431-021-00818-9
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeEngland
dcterms.dateAccepted2021-01-22
dc.rights.embargodate9999-12-31
dc.identifier.eissn1476-5438
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1038/s41431-021-00818-9
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-09
rioxxterms.typeJournal Article/Review


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