TY  - JOUR
AU  - Park, Joohyun
AU  - Koko, Mahmoud
AU  - Hedrich, Ulrike B S
AU  - Hermann, Andreas
AU  - Cremer, Kirsten
AU  - Haberlandt, Edda
AU  - Grimmel, Mona
AU  - Alhaddad, Bader
AU  - Beck-Woedl, Stefanie
AU  - Harrer, Merle
AU  - Karall, Daniela
AU  - Kingelhoefer, Lisa
AU  - Tzschach, Andreas
AU  - Matthies, Lars C
AU  - Strom, Tim M
AU  - Ringelstein, Erich Bernd
AU  - Sturm, Marc
AU  - Engels, Hartmut
AU  - Wolff, Markus
AU  - Lerche, Holger
AU  - Haack, Tobias B
TI  - KCNC1-related disorders: new de novo variants expand the phenotypic spectrum.
JO  - Annals of Clinical and Translational Neurology
VL  - 6
IS  - 7
SN  - 2328-9503
CY  - Chichester [u.a.]
PB  - Wiley
M1  - DZNE-2020-07152
SP  - 1319-1326
PY  - 2019
AB  - 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.
KW  - Animals
KW  - Ataxia: genetics
KW  - Child
KW  - Codon, Nonsense
KW  - Genetic Association Studies
KW  - Humans
KW  - Intellectual Disability: genetics
KW  - Male
KW  - Mutation, Missense
KW  - Myoclonic Epilepsies, Progressive
KW  - Seizures: genetics
KW  - Shaw Potassium Channels: genetics
KW  - Shaw Potassium Channels: physiology
KW  - Xenopus laevis
LB  - PUB:(DE-HGF)16
C6  - pmid:31353862
C2  - pmc:PMC6649617
DO  - DOI:10.1002/acn3.50799
UR  - https://pub.dzne.de/record/140830
ER  -