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

European Journal of Human Genetics (2023)Cite this article

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Abstract

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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Author information

Authors and Affiliations

  1. Department of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University, Muscat, Oman

    Almundher Al-Maawali & Fathiya Al-Murshedi

  2. Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Almundher Al-Maawali & Katta M. Girisha

  3. Department of Child Health, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman

    Amna Al-Futaisi & Ahmed Mansy

  4. Department of Nursing, Sultan Qaboos University Hospital, Muscat, Oman

    Asila Al-Habsi

Authors
  1. Almundher Al-Maawali
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  2. Fathiya Al-Murshedi
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  3. Amna Al-Futaisi
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  4. Ahmed Mansy
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  5. Asila Al-Habsi
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  6. Katta M. Girisha
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Contributions

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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The tests were performed on a clinical basis and consent was obtained from parents for publication of photographs.

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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). https://doi.org/10.1038/s41431-023-01493-8

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  • DOI: https://doi.org/10.1038/s41431-023-01493-8

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