KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine.

Autor: Müller P; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, 72076, Germany., Takacs DS; Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA., Hedrich UBS; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, 72076, Germany., Coorg R; Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA., Masters L; Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA., Glinton KE; Division of Genetics, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA., Dai H; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Baylor Genetics, Houston, Texas, USA., Cokley JA; Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA., Riviello JJ; Division of Neurology and Developmental Neuroscience, Epilepsy and Neurophysiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA., Lerche H; Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, 72076, Germany., Cooper EC; Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: Annals of clinical and translational neurology [Ann Clin Transl Neurol] 2023 Apr; Vol. 10 (4), pp. 656-663. Date of Electronic Publication: 2023 Feb 15.
DOI: 10.1002/acn3.51742
Abstrakt: Precision 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 K V 1.1. 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.
(© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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