Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K<sup>+</sup> channelopathies.

Details

Serval ID
serval:BIB_FB1A5B23DB43
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K<sup>+</sup> channelopathies.
Journal
European journal of human genetics
Author(s)
Gripp K.W., Smithson S.F., Scurr I.J., Baptista J., Majumdar A., Pierre G., Williams M., Henderson L.B., Wentzensen I.M., McLaughlin H., Leeuwen L., Simon MEH, van Binsbergen E., Dinulos MBP, Kaplan J.D., McRae A., Superti-Furga A., Good J.M., Kutsche K.
ISSN
1476-5438 (Electronic)
ISSN-L
1018-4813
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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 <sup>+</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 KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 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 <sup>+</sup> conductance, referred to as syndromic neurodevelopmental K <sup>+</sup> channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2021 10:06
Last modification date
20/03/2021 7:22
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