ArticlePloS one2015
Functional analysis helps to define KCNC3 mutational spectrum in Dutch ataxia cases.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Intellectual Disability and Potassium Channelopathies: A Systematic Review.Frontiers in genetics · 2020Pooled it
- Cerebellar ataxia in the Philippines: a scoping review of reported cases and practical approach.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Proper localization of the SCA13-linked KNeurobiology of disease · 2026Article
- A novel early onset spinocerebellar ataxia 13 BAC mouse model with cerebellar atrophy, tremor, and ataxic gait.Experimental animals · 2025Article
- Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence ofInternational journal of molecular sciences · 2024Article
- A novel KCND3 variant in the N-terminus impairs the ionic current of Kv4.3 and is associated with SCA19/22.Journal of cellular and molecular medicine · 2024Article
- Phenotypical, genotypical and pathological characterization of the moonwalker mouse, a model of ataxia.Neurobiology of disease · 2024Article
- A novelFrontiers in cellular neuroscience · 2024Article
- Voltage-gated potassium channels as a potential therapeutic target for the treatment of neurological and psychiatric disorders.Frontiers in cellular neuroscience · 2024Review
- A missense mutation inProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Feasibility of Follow-Up Studies and Reclassification in Spinocerebellar Ataxia Gene Variants of Unknown Significance.Frontiers in genetics · 2022Article
- Spinocerebellar ataxias (SCAs) caused by common mutations.Neurogenetics · 2021Review
- Spinocerebellar Ataxia 13 Presenting with Pure Cerebellar Syndrome in a Korean Family.Journal of movement disorders · 2020Article
- Article
- KCNC1-related disorders: new de novo variants expand the phenotypic spectrum.Annals of clinical and translational neurology · 2019Article
- C-terminal proline deletions in KCNC3 cause delayed channel inactivation and an adult-onset progressive SCA13 with spasticity.Cerebellum (London, England) · 2018Article
- Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Kv3 Channels: Enablers of Rapid Firing, Neurotransmitter Release, and Neuronal Endurance.Physiological reviews · 2017Review
- Using the shared genetics of dystonia and ataxia to unravel their pathogenesis.Neuroscience and biobehavioral reviews · 2017Review
- Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinocerebellar ataxia type 13 (SCA13) is an autosomal dominantly inherited neurodegenerative disorder of the cerebellum caused by mutations in the voltage gated potassium channel KCNC3. To identify novel pathogenic SCA13 mutations in KCNC3 and to gain insights into the disease prevalence in the Netherlands, we sequenced the entire coding region of KCNC3 in 848 Dutch cerebellar ataxia patients with familial or sporadic origin. We evaluated the pathogenicity of the identified variants by co-segregation analysis and in silico prediction followed by biochemical and electrophysiological studies. We identified 19 variants in KCNC3 including 2 non-coding, 11 missense and 6 synonymous variants. Two missense variants did not co-segregate with the disease and were excluded as potentially disease-causing mutations. We also identified the previously reported p.R420H and p.R423H mutations in our cohort. Of the remaining 7 missense variants, functional analysis revealed that 2 missense variants shifted Kv3.3 channel activation to more negative voltages. These variations were associated with early disease onset and mild intellectual disability. Additionally, one other missense variant shifted channel activation to more positive voltages and was associated with spastic ataxic gait. Whereas, the remaining missense variants did not change any of the channel characteristics. Of these three functional variants, only one variant was in silico predicted to be damaging and segregated with disease. The other two variants were in silico predicted to be benign and co-segregation analysis was not optimal or could only be partially confirmed. Therefore, we conclude that we have identified at least one novel pathogenic mutation in KCNC3 that cause SCA13 and two additionally potential SCA13 mutations. This leads to an estimate of SCA13 prevalence in the Netherlands to be between 0.6% and 1.3%.
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