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Cited by 10Epilepsy research and treatmentPharmacological Effects and Toxicity StudiesGenetics and Neurodevelopmental Disorders

Gene variations of glutamate metabolism pathway and epilepsy

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Feng, Yan, Zhang, Cuirong, Wei, Zihan, Li, Guoyan, Gan, Yajing, Liu, Chao, Deng, Yanchun·2022·Acta Epileptologica
DOI 10.1186/s42494-022-00103-2
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Abstract

Background: Epilepsy is a paroxysmal disorder of the brain, caused by an imbalance of neuronal excitation and inhibition. Glutamate is the most important excitatory neurotransmitter in the brain and plays an important role in epileptogenesis. Mutations in genes at any step/component of the glutamate metabolic pathway may lead to the development of epilepsy or epileptic encephalopathy. Methods: Clinical history of 3 epilepsy patients with genetic variations of the glutamate metabolism pathway was collected. Electroencephalogram recording and magnetic resonance imaging were performed in each patient. We also reviewed recent literature for a variety of the genetic variations involved in epilepsy. Results: Case 1 was a SLC1A2 mutation-carrier diagnosed with developmental and epileptic encephalopathy (DEE) 41, whose seizures decreased after start of the ketogenic diet. Case 2 carried a GRIN2A gene mutation and was seizure-free for three years after taking levetiracetam and vitamin B6. Case 3 was a GRIN2B mutation-carrier diagnosed with DEE 27, who seizures diminished after taking oxcarbazepine. Conclusions: Preclinical and clinical evidence supports the therapeutic potential of glutamatergic signaling-targeting treatments for epilepsy. More studies are needed to discover novel DEE-related genetic mutations in the glutamate metabolic pathway.

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  • Loss or dysfunction of SLC1A2 has been implicated in multiple neurodegenerative and neuropsychiatric disorders, including AD where it is closely associated with cognitive decline.

    “Loss or dysfunction of SLC1A2 has been implicated in multiple neurodegenerative and neuropsychiatric disorders, including AD where it is closely associated with cognitive decline [126–131].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [127]

    The Glutamate transport section links SLC1A2 mutations to developmental epileptic encephalopathy and reports progressive neuronal death in knockout mice. It does not link SLC1A2 to multiple neurodegenerative or neuropsychiatric disorders, Alzheimer’s disease, or cognitive decline. In the Conclusions table, “AD” means autosomal dominant, not Alzheimer’s disease; no page numbers are available in our copy. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Feng, Y., Zhang, C., Wei, Z., Li, G., Gan, Y., Liu, C., & Deng, Y.
Affiliations
  • Xi'an Medical University (CN)
  • Xijing Hospital (CN)
Corresponding author
Deng, Yanchun
ORCID
Venue
Acta Epileptologica
Publisher
Springer Science and Business Media LLC
Published
2022-06-23
Volume
4
Issue
1
ISSN
  • 2096-9384 (ISSN-L)
  • 2524-4434
DOI
10.1186/s42494-022-00103-2
OpenAlex
W4283316102
Cited by
10
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 1 · 2023: 3
FWCI
1.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Epileptologica (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Key research and development program precision medicine project-cohort study (2017YFC0907700)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
epilepsy, glutamate metabolism, genetic mutations, developmental and epileptic encephalopathy, GLT-1, GRIN2A, NR2B subunit, ketogenic diet, levetiracetam, vitamin B6, oxcarbazepine, glutamatergic signaling, epileptogenesis

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