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ATP6V0C gene variants were identified in individuals with epilepsy, with or without developmental delay

Journal of Human Genetics volume 68, pages 589–597 (2023)Cite this article

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Abstract

The cause of epilepsy with or without developmental disorders was unidentified in a significant proportion of patients. Whole exome sequencing was performed in three unrelated patients with early-onset epilepsy, with or without developmental delay and intellectual disability. We identified de novo heterozygous variants (p.Arg119Trp, p.Val99_Ser102del, c.260_263 + 11delinsGCCCA) in the ATP6V0C gene, which encodes a subunit of vacuolar ATPase. Three-dimensional protein modeling showed that the variant p.Arg119Trp in ATP6V0C affected the hydrogen bonds with the 115th and 123rd residues, and the protein stability. The p.Val99_Ser102del and c.260_263 + 11delinsGCCCA variants in the other two patients resulted in a loss of function with microdeletion or splicing effects. Their seizures and psychomotor developmental outcomes were different, and all patients had a good prognosis. Our study provides evidence that de novo heterozygous ATP6V0C variants are related to epilepsy and associated with or without developmental delay.

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Acknowledgements

We appreciate all the patients and their family involved in this study.

Funding

Funding

This work was supported by the CAAE Epilepsy Research Fund (CU-2022-075) and Shanxi Province Social Development science and technology Project (S2016YFSF0214).

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Author notes

  1. These authors contributed equally: Siyu Zhao, Xiaoling Zhang, Le Yang.

Authors and Affiliations

  1. Department of Pediatric neurology, Xi’an Children’s Hospital, Xi’an, China

    Siyu Zhao, Le Yang, Yan Wang, ShanShan Jia, Xia Li, Zhijing Wang & Dong Wang

  2. Department of neurology, The Mine Hospital of Xu Zhou, Xuzhou, China

    Xiaoling Zhang

  3. Cipher Gene LLC, Beijing, China

    Fan Yang & Mengmeng Liang

  4. Department of Pediatric, The Second Hospital of Heibei Medical University, Shijiazhuang, China

    Xiuxia Wang

Authors
  1. Siyu Zhao
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  4. Yan Wang
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  6. Xia Li
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Contributions

SYZ, XXW and DW designed the study, SYZ, XLZ, and LY drafted the manuscript. FY and MML analyzed the genetic data and performed Sanger sequencing. YW, SSJ, XL, and ZJW collected and processed all biological samples, and organize clinical records.

Corresponding authors

Correspondence to Xiuxia Wang or Dong Wang.

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The authors declare no competing interests.

Ethics statement

All patients were well informed and provided written informed consent. This research was approved by the ethics committee of the Xi’an Children’s Hospital.

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Zhao, S., Zhang, X., Yang, L. et al. ATP6V0C gene variants were identified in individuals with epilepsy, with or without developmental delay. J Hum Genet 68, 589–597 (2023). https://doi.org/10.1038/s10038-023-01145-1

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