ArticleThe Journal of physiology2010
Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy.
Article in The Journal of physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Clinical and Radiological Variability in Episodic Ataxia Type 2: A Case Report and Review of the Literature.Cerebellum (London, England) · 2026Review
- From Suspected Congenital Cytomegalovirus Infection to Malan Syndrome: Delayed Genetic Diagnosis Due to Diagnostic Anchoring.Diseases (Basel, Switzerland) · 2026Article
- Postural control in episodic ataxia type 2: no evidence for increased vestibular excitability.European journal of neurology · 2025Article
- Dissociable effects of medication on visual-vestibular brain excitability by visual motion stimuli in episodic ataxia type 2.Brain communications · 2025Article
- Prolonged apnea in a boy with epilepsy and a novel gain-of-function missense CACNA1A variant indicating SUDEP risk.Frontiers in neurology · 2025Article
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- Pin1 promotes human CaCell communication and signaling : CCS · 2024Article
- Intellectual Disability in Episodic Ataxia Type 2: Beyond Paroxysmal Vertigo and Ataxia.Journal of clinical neurology (Seoul, Korea) · 2024Article
- A Review of theDiseases (Basel, Switzerland) · 2024Review
- Intrafamilial neurological phenotypic variability due to either biallelic or monoallelic pathogenic variants inFrontiers in neurology · 2024Article
- Rare genetic brain disorders with overlapping neurological and psychiatric phenotypes.Nature reviews. Neurology · 2024Review
- Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders.Membranes · 2023Article
- The genotype-phenotype correlations of theFrontiers in molecular neuroscience · 2023Article
- CACNA1A-Related Channelopathies: Clinical Manifestations and Treatment Options.Handbook of experimental pharmacology · 2023Review
- Hippocampus-related cognitive disorders develop in the absence of epilepsy and ataxia in the heterozygousChannels (Austin, Tex.) · 2022Article
- Review
- Towards Zebrafish Models of CNS Channelopathies.International journal of molecular sciences · 2022Review
- The complexities of CACNA1A in clinical neurogenetics.Journal of neurology · 2022Article
- Epilepsy and episodic ataxia type 2: family study and review of the literature.Journal of neurology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in CACNA1A, which encodes the principal subunit of the P/Q calcium channel, underlie episodic ataxia type 2 (EA2). In addition, some patients with episodic ataxia complicated by epilepsy have been shown to harbour CACNA1A mutations, raising the possibility that P/Q channel dysfunction may be linked to human epilepsy. We undertook a review of all published CACNA1A EA2 cases and this showed that 7% have epilepsy--representing a sevenfold increased epilepsy risk compared to the background population risk (P<0.001). We also studied a series of 17 individuals with episodic ataxia accompanied by epilepsy and/or clearly epileptiform electroencephalograms (EEGs). We screened the entire coding region of CACNA1A for point mutations and rearrangements to determine if genetic variation in the gene is associated with the epilepsy phenotype, and measured the functional impact of all missense variations on heterologously expressed P/Q channels. We identified two large scale deletions and two new missense mutations in CACNA1A. When expressed, L621R had little detectable effect on P/Q channel function, while the other missense change, G540R, caused an approximately 30% reduction in current density. In nine patients we also identified the previously reported non-synonymous coding variants (E921D and E993V) which also resulted in impairment of P/Q channel function. Taken together, 12 of the 17 patients have genetic changes which decrease P/Q channel function. We conclude that variants in the coding region of CACNA1A that confer a loss of P/Q-type channel function are associated with episodic ataxia and epilepsy. Our data suggest that functional stratification of all variants, including common polymorphisms, rare variants and novel mutations, may provide new insights into the mechanisms of channelopathies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.