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Novel GATOR1 variants in focal epilepsy
Maša Kovačević1, Milena Janković2, Marija Branković3
1Neurology Clinic, University Clinical Center of Serbia, Serbia; Faculty of Medicine, University of Belgrade, Serbia.
Epilepsy & Behavior : E&B
|February 27, 2023
Summary
Genetic testing of GATOR1 genes identified novel likely pathogenic variants in 3.1% of focal epilepsy patients. This finding aids in identifying individuals for precision medicine approaches in epilepsy treatment.
Area of Science:
- Genetics
- Neurology
- Epilepsy
Background:
- Variants in GATOR1 genes are linked to focal epilepsy syndromes.
- GATOR1 variants are associated with drug-resistant epilepsy and sudden unexplained death in epilepsy.
- Identifying patients for genetic testing and precision medicine is crucial.
Purpose of the Study:
- Determine the diagnostic yield of GATOR1 gene sequencing in focal epilepsy patients.
- Identify novel GATOR1 variants.
- Characterize variant carriers clinically, electroencephalographically, and radiologically.
Main Methods:
- Sequenced DEPDC5, NPRL2, and NPRL3 genes in 96 patients with suspected genetic focal epilepsy.
- Classified variants of interest (VOI) using ACMG-AMP criteria.
Main Results:
- Identified 4 previously unreported VOI in 4.2% of patients.
- Found 3 likely pathogenic variants in 3.1% of patients, including novel DEPDC5 and NPRL2 variants.
- One VOI in NPRL3 was classified as a variant of unknown significance.
Conclusions:
- GATOR1 gene sequencing yielded a diagnosis in 3.1% of cases, identifying three novel likely pathogenic variants.
- A novel association between temporal lobe epilepsy with hippocampal sclerosis and an NPRL2 variant was discovered.
- Further research is needed to fully understand the clinical spectrum of GATOR1 gene-associated epilepsy.
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