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XB-ART-56998
Ann Clin Transl Neurol January 1, 2019; 6 (7): 1319-1326.

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

Park J , Koko M , Hedrich UBS , Hermann A , Cremer K , Haberlandt E , Grimmel M , Alhaddad B , Beck-Woedl S , Harrer M , Karall D , Kingelhoefer L , Tzschach A , Matthies LC , Strom TM , Ringelstein EB , Sturm M , Engels H , Wolff M , Lerche H , Haack TB .


Abstract
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.

PubMed ID: 31353862
PMC ID: PMC6649617
Article link: Ann Clin Transl Neurol
Grant support: [+]

Species referenced: Xenopus
Genes referenced: kcnc1 kcnc2 kcnc4
GO keywords: potassium channel activity

Disease Ontology terms: progressive myoclonus epilepsy 7 [+]
OMIMs: MYOCLONIC EPILEPSY OF UNVERRICHT AND LUNDBORG [+]

Article Images: [+] show captions
References [+] :
Aggarwal, Contribution of the S4 segment to gating charge in the Shaker K+ channel. 1996, Pubmed, Xenbase