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Biallelic variants in the synaptic vesicle glycoprotein 2 A are associated with epileptic encephalopathy


Synaptic Vesicle Glycoprotein 2 A (SV2A) is a membrane protein of synaptic vesicles and the binding site of antiepileptic drug levetiracetam. Biallelic Arg383Gln is reported in a family with intractable epilepsy earlier. Here, we report on the second family with early onset drug resistant epilepsy. We identified homozygous Arg289Ter variant by exome sequencing that segregated with the phenotype in the family. The affected children in these two families are normal at birth and developed recurrent seizures beginning in the second month of life and developed secondary failure of growth and development. Knock out mice models earlier had replicated the human phenotype observed in these two families. These findings support that biallelic loss of function variants in SV2A result in early onset intractable epilepsy in humans.

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Fig. 1: Pedigree of the family and segregation of the variant.

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Data available on request from the authors


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Authors and Affiliations



AAM: concept and identification of the variant by exome analysis and drafting the first version of the manuscript. FAM: concept and clinical evaluation of the patient and data analysis. AAF, AM, AAH: clinical data collection and concept. KMG: concept, and critical revision of the first version. All authors have edited the manuscript drafts and revisions and approved the final version of the manuscript.

Corresponding author

Correspondence to Katta M. Girisha.

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The authors declare no competing interests.

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Al-Maawali, A., Al-Murshedi, F., Al-Futaisi, A. et al. Biallelic variants in the synaptic vesicle glycoprotein 2 A are associated with epileptic encephalopathy. Eur J Hum Genet (2023).

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