Clinical heterogeneity associated with KCNA1 mutations include cataplexy and nonataxic presentations
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Author(s)
Brownstein, Catherine A.
Beggs, Alan H.
Rodan, Lance
Shi, Jiahai
Towne, Meghan C.
Pelletier, Renee
Cao, Siqi
Rosenberg, Paul A.
Urion, David K.
Picker, Jonathan
Date Issued
September 2015
Journal
neurogenetics
Publisher
Springer Berlin Heidelberg
Citation
Brownstein, Catherine A., Alan H. Beggs, Lance Rodan, Jiahai Shi, Meghan C. Towne, Renee Pelletier, Siqi Cao, et al. “Clinical Heterogeneity Associated with KCNA1 Mutations Include Cataplexy and Nonataxic Presentations.” Neurogenetics 17, no. 1 (September 22, 2015): 11–16.
Version
Author's final manuscript
Abstract
Mutations in the KCNA1 gene are known to cause episodic ataxia/myokymia syndrome type 1 (EA1). Here, we describe two families with unique presentations who were enrolled in an IRB-approved study, extensively phenotyped, and whole exome sequencing (WES) performed. Family 1 had a diagnosis of isolated cataplexy triggered by sudden physical exertion in multiple affected individuals with heterogeneous neurological findings. All enrolled affected members carried a KCNA1 c.941T>C (p.I314T) mutation. Family 2 had an 8-year-old patient with muscle spasms with rigidity for whom WES revealed a previously reported heterozygous missense mutation in KCNA1 c.677C>G (p.T226R), confirming the diagnosis of EA1 without ataxia. WES identified variants in KCNA1 that explain both phenotypes expanding the phenotypic spectrum of diseases associated with mutations of this gene. KCNA1 mutations should be considered in patients of all ages with episodic neurological phenotypes, even when ataxia is not present. This is an example of the power of genomic approaches to identify pathogenic mutations in unsuspected genes responsible for heterogeneous diseases.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1007/s10048-015-0460-2
