Department of Pediatric neurology, Xi'an Children's Hospital, Xi'an, China.
Department of neurology, The Mine Hospital of Xu Zhou, Xuzhou, China.
J Hum Genet. 2023 Sep;68(9):589-597. doi: 10.1038/s10038-023-01145-1. Epub 2023 May 10.
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 115 and 123 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.
在很大一部分患者中，伴有或不伴有发育障碍的癫痫病因不明。对 3 名患有早发性癫痫、伴有或不伴有发育迟缓及智力障碍的无关联患者进行了全外显子组测序。我们在 ATP6V0C 基因中发现了新生杂合变异（p.Arg119Trp、p.Val99_Ser102del、c.260_263 + 11delinsGCCCA），该基因编码液泡型三磷酸腺苷酶的一个亚基。三维蛋白建模显示，ATP6V0C 中的变异 p.Arg119Trp 影响与 115 和 123 位残基的氢键以及蛋白稳定性。另外 2 名患者中的 p.Val99_Ser102del 和 c.260_263 + 11delinsGCCCA 变异导致功能丧失，出现微缺失或剪接效应。他们的癫痫发作和精神运动发育结果不同，所有患者的预后均良好。本研究提供了证据表明，新生杂合 ATP6V0C 变异与癫痫有关，并且与发育迟缓有关或无关。
