SLC6A1 Mutation and Ketogenic Diet in Epilepsy With Myoclonic-Atonic Seizures.

Autor: Palmer S; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Towne MC; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Pearl PL; Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Pelletier RC; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Genetti CA; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Shi J; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR., Beggs AH; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Agrawal PB; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; Division of Newborn Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts., Brownstein CA; Division of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; The Manton Center for Orphan Disease Research, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: Catherine.brownstein@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Pediatric neurology [Pediatr Neurol] 2016 Nov; Vol. 64, pp. 77-79. Date of Electronic Publication: 2016 Jul 28.
DOI: 10.1016/j.pediatrneurol.2016.07.012
Abstrakt: Background: Epilepsy with myoclonic-atonic seizures, also known as myoclonic-astatic epilepsy or Doose syndrome, has been recently linked to variants in the SLC6A1 gene. Epilepsy with myoclonic-atonic seizures is often refractory to antiepileptic drugs, and the ketogenic diet is known for treating medically intractable seizures, although the mechanism of action is largely unknown. We report a novel SLC6A1 variant in a patient with epilepsy with myoclonic-atonic seizures, analyze its effects, and suggest a mechanism of action for the ketogenic diet.
Methods: We describe a ten-year-old girl with epilepsy with myoclonic-atonic seizures and a de novo SLC6A1 mutation who responded well to the ketogenic diet. She carried a c.491G>A mutation predicted to cause p.Cys164Tyr amino acid change, which was identified using whole exome sequencing and confirmed by Sanger sequencing. High-resolution structural modeling was used to analyze the likely effects of the mutation.
Results: The SLC6A1 gene encodes a transporter that removes gamma-aminobutyric acid from the synaptic cleft. Mutations in SLC6A1 are known to disrupt the gamma-aminobutyric acid transporter protein 1, affecting gamma-aminobutyric acid levels and causing seizures. The p.Cys164Tyr variant found in our study has not been previously reported, expanding on the variants linked to epilepsy with myoclonic-atonic seizures.
Conclusion: A 10-year-old girl with a novel SLC6A1 mutation and epilepsy with myoclonic-atonic seizures had an excellent clinical response to the ketogenic diet. An effect of the diet on gamma-aminobutyric acid reuptake mediated by gamma-aminobutyric acid transporter protein 1 is suggested. A personalized approach to epilepsy with myoclonic-atonic seizures patients carrying SLC6A1 mutation and a relationship between epilepsy with myoclonic-atonic seizures due to SLC6A1 mutations, GABAergic drugs, and the ketogenic diet warrants further exploration.
(Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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