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Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy

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Abstract

Ion channels are crucial in the generation and modulation of excitability in the nervous system and have been implicated in human epilepsy. Forty-one epilepsy-associated ion channel genes and their mutations are systematically reviewed. In this paper, we analyzed the genotypes, functional alterations (funotypes), and phenotypes of these mutations. Eleven genes featured loss-of-function mutations and six had gain-of-function mutations. Nine genes displayed diversified funotypes, among which a distinct funotype-phenotype correlation was found in SCN1A. These data suggest that the funotype is an essential consideration in evaluating the pathogenicity of mutations and a distinct funotype or funotype-phenotype correlation helps to define the pathogenic potential of a gene.

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Acknowledgements

Research work from our laboratory cited in this review was supported by the National Natural Science Foundation of China (81571273, 81571274, 81501124, 81271434, and 81301107), Omics-based precision medicine of epilepsy being entrusted by Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400), the Natural Science Foundation of Guangdong Province, China (2014A030313489), Science and Technology Planning Projects of Guangdong Province, China (2012B031800404 and 2013B051000084), the Department of Education of Guangdong Province, China (2013CXZDA022, 2013KJCX0156, and 2012KJCX009), the Foundation for High-level Talents in Higher Education of Guangdong Province, China (2013-167), Yangcheng Scholar Research Projects of Guangzhou Municipal College (12A016S and 12A017G), and Science and Technology Projects of Guangzhou, Guangdong Province, China (2014J4100069, 201508020011, 201604020161, and 201607010002).

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  1. Feng Wei and Li-Min Yan have contributed equally to this work.

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  1. Institute of Neuroscience, Department of Neurology of The Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and Ministry of Education of China, Guangzhou Medical University, Guangzhou, 510260, China

    Feng Wei, Li-Min Yan, Tao Su, Na He, Zhi-Jian Lin, Jie Wang, Yi-Wu Shi, Yong-Hong Yi & Wei-Ping Liao

  2. Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, China

    Feng Wei

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Wei, F., Yan, LM., Su, T. et al. Ion Channel Genes and Epilepsy: Functional Alteration, Pathogenic Potential, and Mechanism of Epilepsy. Neurosci. Bull. 33, 455–477 (2017). https://doi.org/10.1007/s12264-017-0134-1

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