ArticleAnnals of neurology2012
Mutations in KCND3 cause spinocerebellar ataxia type 22.
Article in Annals of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.European journal of human genetics : EJHG · 2019Pooled it
- Insights from cerebellar transcriptomic analysis into the pathogenesis of ataxia.JAMA neurology · 2014Trial
- Parkinsonism with Reduced Striatal Uptake on DAT-SPECT in a Patient Harboring a Novel KCND3 Variant.Cerebellum (London, England) · 2026Review
- Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology.Medical review (2021) · 2025Review
- Restoration of Shal/KCellular and molecular life sciences : CMLS · 2025Article
- Functional characterization of two KCND3 variants associated with SCA 19/22 ataxia in Latin American families.Biological research · 2025Article
- Characterizing molecular and behavioral changes arising from ROMK potassium channel deficiency in the cerebellum.Frontiers in behavioral neuroscience · 2025Article
- A dominant negative Kcnd3 F227del mutation in mice causes spinocerebellar ataxia type 22 (SCA22) by impairing ER and Golgi functioning.The Journal of pathology · 2025Article
- Genes to therapy: a comprehensive literature review of whole-exome sequencing in neurology and neurosurgery.European journal of medical research · 2024Review
- 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
- Parkinsonism in SCA19/22: Dopamine Transporter Imaging in an Italian Family Harboring a Novel Mutation.Cerebellum (London, England) · 2024Article
- Potential Benefit of Channel Activators in Loss-of-Function Primary Potassium Channelopathies Causing Heredoataxia.Cerebellum (London, England) · 2024Review
- Oxidative stress and ion channels in neurodegenerative diseases.Frontiers in physiology · 2024Review
- An E280K Missense Variant inInternational journal of molecular sciences · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- Pediatric-Onset Epilepsy and Developmental Epileptic Encephalopathies Followed by Early-Onset Parkinsonism.International journal of molecular sciences · 2023Review
- Electrophysiology of ataxia-telangiectasia-like disorder 1.Sudanese journal of paediatrics · 2023Article
- Diagnostic Efficacy of Genetic Studies in a Series of Hereditary Cerebellar Ataxias in Eastern Spain.Neurology. Genetics · 2022Article
- A Second Case With the V374ANeurology. Genetics · 2022Article
- The Regulation of MiTF/TFE Transcription Factors Across Model Organisms: from Brain Physiology to Implication for Neurodegeneration.Molecular neurobiology · 2022Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
Abstract
objectiveTo identify the causative gene in spinocerebellar ataxia (SCA) 22, an autosomal dominant cerebellar ataxia mapped to chromosome 1p21-q23.
methodsWe previously characterized a large Chinese family with progressive ataxia designated SCA22, which overlaps with the locus of SCA19. The disease locus in a French family and an Ashkenazi Jewish American family was also mapped to this region. Members from all 3 families were enrolled. Whole exome sequencing was performed to identify candidate mutations, which were narrowed by linkage analysis and confirmed by Sanger sequencing and cosegregation analyses. Mutational analyses were also performed in 105 Chinese and 55 Japanese families with cerebellar ataxia. Mutant gene products were examined in a heterologous expression system to address the changes in protein localization and electrophysiological functions.
resultsWe identified heterozygous mutations in the voltage-gated potassium channel Kv4.3-encoding gene KCND3: an in-frame 3-nucleotide deletion c.679_681delTTC p.F227del in both the Chinese and French pedigrees, and a missense mutation c.1034G>T p.G345V in the Ashkenazi Jewish family. Direct sequencing of KCND3 further identified 3 mutations, c.1034G>T p.G345V, c.1013T>C p.V338E, and c.1130C>T p.T377M, in 3 Japanese kindreds. Immunofluorescence analyses revealed that the mutant p.F227del Kv4.3 subunits were retained in the cytoplasm, consistent with the lack of A-type K(+) channel conductance in whole cell patch-clamp recordings.
interpretationOur data identify the cause of SCA19/22 in patients of diverse ethnic origins as mutations in KCND3. These findings further emphasize the important role of ion channels as key regulators of neuronal excitability in the pathogenesis of cerebellar degeneration.
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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.