Center of Excellence for Medical Genomics, Medical Genomics Cluster, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok 10330, Thailand.
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Brain Dev. 2021 Mar;43(3):490-494. doi: 10.1016/j.braindev.2020.10.016. Epub 2020 Nov 13.
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.
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.
Trio whole-exome sequencing was performed and revealed a novel de novo heterozygous stop-loss c.467A > T (p.156Leuext35) 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.
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.
约有一半的癫痫伴智力障碍（ID）患者病因不明，可能是新疾病基因的突变。
为了确定一名癫痫伴 ID 女性患者的致病突变，我们进行了三人体外全基因组测序、逆转录聚合酶链反应（RT-PCR）后行 Sanger 测序。
进行了三人体外全基因组测序，发现 ATP6V0C 基因中存在一个新的杂合性无义突变 c.467A>T（p.156Leuext35）。用白细胞 RNA 进行 RT-PCR 后行 Sanger 测序显示存在突变 RNA，实时 PCR 显示患者的 ATP6V0C RNA 水平约为其父母的一半，提示杂合性不足为一种发病机制。
这些发现以及先前报道的具有相同表型和相同基因变异的个体证实了 ATP6V0C 是引起癫痫伴 ID 的一个基因。
