Novel de novo mutation substantiates ATP6V0C as a gene causing epilepsy with intellectual disability

Background: In approximately half of patients with epilepsy and intellectual disability (ID), the cause is unidentified and could be a mutation in a new disease gene. Patient description: To determine the discovery of disease-causing mutation in a female patient with epilepsy and ID, we performed trio whole-exome sequencing, reverse transcription polymerase chain reaction (RT-PCR) followed by Sanger sequencing. Results: Trio whole-exome sequencing was performed and revealed a novel de novo heterozygous stop-loss c.467A > T (p. *156Leuext*35) mutation in the ATP6V0C gene. Using RNA from leukocytes, RT-PCR followed by Sanger sequencing showed the existence of the mutant RNA, and real-time PCR demonstrated that the patient's ATP6V0C RNA level was approximately half of that in her parents, suggesting haploinsufficiency as a pathomechanism. Conclusion: These findings, along with previous reports of individuals with similar phenotypes and variants in the same gene, substantiate ATP6V0C as a gene causing epilepsy with ID. (c) 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.