<i>KCNA1</i> gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine-Reference-Cited by-同舟云学术

KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine

Published:2023-02-15 Issue:4 Volume:10 Page:656-663
ISSN:2328-9503
Container-title:Annals of Clinical and Translational Neurology
language:en
Short-container-title:Ann Clin Transl Neurol

Author:

Müller Peter¹,Takacs Danielle S.²³,Hedrich Ulrike B. S.¹,Coorg Rohini²³,Masters Laura²³,Glinton Kevin E.⁴⁵,Dai Hongzheng⁵⁶,Cokley Jon A.²,Riviello James J.²³,Lerche Holger¹,Cooper Edward C.³⁵⁷^ORCID

Affiliation:

1. Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research University of Tuebingen Tuebingen 72076 Germany

2. Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics Texas Children's Hospital, Baylor College of Medicine Houston Texas USA

3. Department of Neurology Baylor College of Medicine Houston Texas USA

4. Division of Genetics, Department of Pediatrics Texas Children's Hospital, Baylor College of Medicine Houston Texas USA

5. Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas USA

6. Baylor Genetics Houston Texas USA

7. Department of Neuroscience Baylor College of Medicine Houston Texas USA

Abstract

AbstractPrecision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage‐gated K+ channel subunit KV1.1. So far, loss‐of‐function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain‐of‐function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4‐aminopyridine. Clinical use of 4‐aminopyridine was associated with reduced seizure burden, enabled simplification of co‐medication and prevented rehospitalization.

Funder

Deutsche Forschungsgemeinschaft

National Institute of Neurological Disorders and Stroke

Publisher

Wiley

Subject

Neurology (clinical),General Neuroscience

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/acn3.51742

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