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KCNC1-related disorders: New de novo variants expand the phenotypic spectrum
- Source :
- Ann. Clin. Transl. Neurol. 6, 1319-1326 (2019), Annals of Clinical and Translational Neurology 6(7), 1319-1326 (2019). doi:10.1002/acn3.50799, Annals of Clinical and Translational Neurology, Vol 6, Iss 7, Pp 1319-1326 (2019), Annals of Clinical and Translational Neurology
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
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.
- Subjects :
- Male
Mutation, Missense
Neurosciences. Biological psychiatry. Neuropsychiatry
Brief Communication
Xenopus laevis
Seizures
physiology [Shaw Potassium Channels]
Intellectual Disability
Animals
Humans
ddc:610
RC346-429
Child
Genetic Association Studies
genetics [Shaw Potassium Channels]
genetics [Ataxia]
Myoclonic Epilepsies, Progressive
genetics [Seizures]
Shaw Potassium Channels
Codon, Nonsense
Ataxia
Neurology. Diseases of the nervous system
genetics [Intellectual Disability]
Brief Communications
RC321-571
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Ann. Clin. Transl. Neurol. 6, 1319-1326 (2019), Annals of Clinical and Translational Neurology 6(7), 1319-1326 (2019). doi:10.1002/acn3.50799, Annals of Clinical and Translational Neurology, Vol 6, Iss 7, Pp 1319-1326 (2019), Annals of Clinical and Translational Neurology
- Accession number :
- edsair.pmid.dedup....d3d4acb026b42a192bc809ac6e0e1676