PuSH - Publication Server of Helmholtz Zentrum München

Park, J.* ; Koko, M.* ; Hedrich, U.B.S.* ; Hermann, A.* ; Cremer, K.* ; Haberlandt, E.* ; Grimmel, M.* ; Alhaddad, B. ; Beck-Woedl, S.* ; Harrer, M.* ; Karall, D.* ; Kingelhoefer, L.* ; Tzschach, A.* ; Matthies, L.C.* ; Strom, T.M. ; Ringelstein, E.B.* ; Sturm, M.* ; Engels, H.* ; Wolff, M.* ; Lerche, H.* ; Haack, T.B.*

KCNC1-related disorders: New de novo variants expand the phenotypic spectrum.

Ann. Clin. Transl. Neurol. 6, 1319-1326 (2019)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
A recurrent de novo missense variant in KCNC1, encoding a voltage-gated potassium channel expressed in inhibitory neurons, causes progressive myoclonus epilepsy and ataxia, and a nonsense variant is associated with intellectual disability. We identified three new de novo missense variants in KCNC1 in five unrelated individuals causing different phenotypes featuring either isolated nonprogressive myoclonus (p.Cys208Tyr), intellectual disability (p.Thr399Met), or epilepsy with myoclonic, absence and generalized tonic-clonic seizures, ataxia, and developmental delay (p.Ala421Val, three patients). Functional analyses demonstrated no measurable currents for all identified variants and dominant-negative effects for p.Thr399Met and p.Ala421Val predicting neuronal disinhibition as the underlying disease mechanism.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Intellectual Disability; Mutations; Epilepsy; Channel; Kcnc1
ISSN (print) / ISBN 2328-9503
e-ISSN 2328-9503
Journal Annals of Clinical and Translational Neurology
Quellenangaben Volume: 6, Issue: 7, Pages: 1319-1326 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Chichester [u.a.]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)