Next Article in Journal
Chrysanthemi Zawadskii var. Latilobum Attenuates Obesity-Induced Skeletal Muscle Atrophy via Regulation of PRMTs in Skeletal Muscle of Mice
Next Article in Special Issue
Kv1.1 Channelopathies: Pathophysiological Mechanisms and Therapeutic Approaches
Previous Article in Journal
Application of Solid-State Nanopore in Protein Detection
Previous Article in Special Issue
Non-Invasive Cerebellar Stimulation in Neurodegenerative Ataxia: A Literature Review
Open AccessReview

Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity

Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(8), 2802; https://doi.org/10.3390/ijms21082802
Received: 31 March 2020 / Revised: 14 April 2020 / Accepted: 16 April 2020 / Published: 17 April 2020
Mutations in the KCNA1 gene, which encodes voltage-gated Kv1.1 potassium channel α-subunits, cause a variety of human diseases, complicating simple genotype–phenotype correlations in patients. KCNA1 mutations are primarily associated with a rare neurological movement disorder known as episodic ataxia type 1 (EA1). However, some patients have EA1 in combination with epilepsy, whereas others have epilepsy alone. KCNA1 mutations can also cause hypomagnesemia and paroxysmal dyskinesia in rare cases. Why KCNA1 variants are associated with such phenotypic heterogeneity in patients is not yet understood. In this review, literature databases (PubMed) and public genetic archives (dbSNP and ClinVar) were mined for known pathogenic or likely pathogenic mutations in KCNA1 to examine whether patterns exist between mutation type and disease manifestation. Analyses of the 47 deleterious KCNA1 mutations that were identified revealed that epilepsy or seizure-related variants tend to cluster in the S1/S2 transmembrane domains and in the pore region of Kv1.1, whereas EA1-associated variants occur along the whole length of the protein. In addition, insights from animal models of KCNA1 channelopathy were considered, as well as the possible influence of genetic modifiers on disease expressivity and severity. Elucidation of the complex relationship between KCNA1 variants and disease will enable better diagnostic risk assessment and more personalized therapeutic strategies for KCNA1 channelopathy. View Full-Text
Keywords: episodic ataxia; epilepsy; KCNA1; Kv1.1 episodic ataxia; epilepsy; KCNA1; Kv1.1
Show Figures

Figure 1

MDPI and ACS Style

Paulhus, K.; Ammerman, L.; Glasscock, E. Clinical Spectrum of KCNA1 Mutations: New Insights into Episodic Ataxia and Epilepsy Comorbidity. Int. J. Mol. Sci. 2020, 21, 2802.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop